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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">OL</journal-id>
<journal-title-group>
<journal-title>Oncology Letters</journal-title>
</journal-title-group>
<issn pub-type="ppub">1792-1074</issn>
<issn pub-type="epub">1792-1082</issn>
<publisher>
<publisher-name>D.A. Spandidos</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3892/ol.2025.15127</article-id>
<article-id pub-id-type="publisher-id">OL-30-2-15127</article-id>
<article-categories>
<subj-group>
<subject>Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Blood MALT1 expression levels reflect the lymph node stage and disease-free survival in patients with non-small cell lung cancer </article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Fengyi</given-names></name>
<xref rid="af1-ol-30-2-15127" ref-type="aff">1</xref></contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Xinping</given-names></name>
<xref rid="af2-ol-30-2-15127" ref-type="aff">2</xref>
<xref rid="c1-ol-30-2-15127" ref-type="corresp"/></contrib>
<contrib contrib-type="author"><name><surname>Wen</surname><given-names>Bing</given-names></name>
<xref rid="af1-ol-30-2-15127" ref-type="aff">1</xref></contrib>
<contrib contrib-type="author"><name><surname>Peng</surname><given-names>Xiaoqin</given-names></name>
<xref rid="af2-ol-30-2-15127" ref-type="aff">2</xref></contrib>
</contrib-group>
<aff id="af1-ol-30-2-15127"><label>1</label>Department of Thoracic Surgery, North Sichuan Medical University, Nanchong, Sichuan 637000, P.R. China</aff>
<aff id="af2-ol-30-2-15127"><label>2</label>Department of Oncology, North Sichuan Medical University, Nanchong, Sichuan 637000, P.R. China</aff>
<author-notes>
<corresp id="c1-ol-30-2-15127"><italic>Correspondence to</italic>: Dr Xinping Zhang, Department of Oncology, North Sichuan Medical University, 97 Renmin Road, Nanchong, Sichuan 637000, P.R. China, E-mail: <email>zhangxinnping@163.com</email></corresp>
</author-notes>
<pub-date pub-type="collection"><month>08</month><year>2025</year></pub-date>
<pub-date pub-type="epub"><day>03</day><month>06</month><year>2025</year></pub-date>
<volume>30</volume>
<issue>2</issue>
<elocation-id>381</elocation-id>
<history>
<date date-type="received"><day>01</day><month>04</month><year>2024</year></date>
<date date-type="accepted"><day>10</day><month>02</month><year>2025</year></date>
</history>
<permissions>
<copyright-statement>Copyright: &#x00A9; 2025 Zhang et al.</copyright-statement>
<copyright-year>2025</copyright-year>
<license license-type="open-access">
<license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by-nc-nd/4.0/">Creative Commons Attribution-NonCommercial-NoDerivs License</ext-link>, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.</license-p></license>
</permissions>
<abstract>
<p>Mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1) promotes cancer development via both cancer cell-intrinsic and -extrinsic mechanisms, and can regulate cancer immunity and immune escape. Therefore, the present study aimed to assess the expression levels of MALT1 in blood samples and the association with clinical features, treatment options and survival outcomes in patients with non-small cell lung cancer (NSCLC). Peripheral blood mononuclear cells (PBMCs) from a total of 125 patients with resectable NSCLC prior to treatment (neoadjuvant therapy or surgery) were collected. The mRNA expression levels of MALT1 were detected by reverse transcription-quantitative PCR. Furthermore, the PBMC samples from 20 healthy individuals served as the control group. The results showed that MALT1 was upregulated in the blood samples of patients with NSCLC compared with the control group (&#x007E;3.4:1 fold; P&#x003C;0.001). Subsequently, for correlation analysis, blood MALT1 expression levels in patients with NSCLC were categorized into four grades according to the quartiles (Q1, Q2, Q3 and Q4). It was indicated that the MALT1 quartile was positively correlated with the tumor-node-metastasis (P=0.036) and N stage (P=0.026), and it had a tendency to be correlated with poor differentiation (P=0.091) and T stage (P=0.058), but this did not reach statistical significance. However, the MALT1 quartile was not associated with neoadjuvant therapy, surgical type or adjuvant therapy. Kaplan-Meier curves demonstrated that the MALT1 quartile was notably associated with shorter disease-free survival (DFS; P=0.009); however, the MALT1 quartile only showed a tendency to be associated with poor overall survival, but this did not reach statistical significance (P=0.118). Subsequent multivariate Cox analysis showed that the MALT1 quartile could independently predict shorter DFS (P=0.016). In conclusion, the present study suggested that blood MALT1 expression levels could potentially predict the stage of lymph node metastasis and DFS in patients with NSCLC.</p>
</abstract>
<kwd-group>
<kwd>mucosa-associated lymphoid tissue lymphoma translocation protein-1</kwd>
<kwd>non-small cell lung cancer</kwd>
<kwd>clinical features</kwd>
<kwd>treatment options</kwd>
<kwd>survival outcomes</kwd>
</kwd-group>
<funding-group>
<award-group>
<funding-source>Nanchong City School Cooperation Special Project</funding-source>
<award-id>19SXH0353</award-id>
</award-group>
<funding-statement>The present study was supported by Nanchong City School Cooperation Special Project (grant no. 19SXH0353).</funding-statement>
</funding-group>
</article-meta>
</front>
<body>
<sec sec-type="intro">
<title>Introduction</title>
<p>Lung cancer, a common fatal malignancy, contributes to 2.21 million new cancer cases and 1.80 million new cancer-related deaths annually worldwide (<xref rid="b1-ol-30-2-15127" ref-type="bibr">1</xref>). In China, 0.83 million new lung cancer cases and 0.66 million new lung cancer-related deaths are recorded every year (<xref rid="b2-ol-30-2-15127" ref-type="bibr">2</xref>), thus causing heavy burdens to the patients and society (<xref rid="b3-ol-30-2-15127" ref-type="bibr">3</xref>,<xref rid="b4-ol-30-2-15127" ref-type="bibr">4</xref>). Non-small cell lung cancer (NSCLC) accounts for &#x007E;85&#x0025; of lung cancer cases in China, thus giving an opportunity for research and development (<xref rid="b5-ol-30-2-15127" ref-type="bibr">5</xref>). Along with the advances in molecular detection technology and big-data gathering and analysis, biomarker-based precision therapy is considered an effective approach to improve prognosis and reduce disease burden in patients with NSCLC (<xref rid="b6-ol-30-2-15127" ref-type="bibr">6</xref>&#x2013;<xref rid="b8-ol-30-2-15127" ref-type="bibr">8</xref>). However, the detection of a large proportion of predictive biomarkers requires the isolation of tissue lesions, which is not always feasible, particularly in patients who cannot undergo surgery.</p>
<p>Mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1), acting as a scaffolding gene/protein that triggers the activation of NF-&#x03BA;B transcription factors and as a protease to modify immune activation-related signaling via diversified substrate cleavage, was recently discovered to facilitate cancer development via both cancer cell-intrinsic and -extrinsic mechanisms (<xref rid="b9-ol-30-2-15127" ref-type="bibr">9</xref>,<xref rid="b10-ol-30-2-15127" ref-type="bibr">10</xref>). MALT1 has been reported to promote cancer cell viability, migration, invasion and drug resistance, and particularly resistance to immune checkpoint inhibitors, in several malignancies, such as breast cancer, prostate cancer, hepatocellular carcinoma and lymphomas (<xref rid="b11-ol-30-2-15127" ref-type="bibr">11</xref>&#x2013;<xref rid="b15-ol-30-2-15127" ref-type="bibr">15</xref>). Previous studies have also demonstrated that MALT1 was upregulated and associated with poor prognosis in patients with colorectal cancer, malignant melanoma and lymphomas (<xref rid="b16-ol-30-2-15127" ref-type="bibr">16</xref>&#x2013;<xref rid="b18-ol-30-2-15127" ref-type="bibr">18</xref>). In terms of lung cancer, MALT1 could promote cancer progression via interacting with caspase recruitment domain-coiled-coil complexes and NF-&#x03BA;B activation (<xref rid="b19-ol-30-2-15127" ref-type="bibr">19</xref>,<xref rid="b20-ol-30-2-15127" ref-type="bibr">20</xref>). Apart from the aforementioned direct regulation of cancer by MALT1, other studies indicated that MALT1 could regulate cancer immunity to promote cancer progression (<xref rid="b15-ol-30-2-15127" ref-type="bibr">15</xref>,<xref rid="b21-ol-30-2-15127" ref-type="bibr">21</xref>). These findings supported the potential of MALT1 expression levels as a prognostic biomarker in patients with NSCLC.</p>
<p>Therefore, the present study aimed to investigate the utility of the expression levels of MALT1 in blood samples from patients with NSCLC and their association with the clinical features, treatment options and survival outcomes for these patients.</p>
</sec>
<sec sec-type="subjects|methods">
<title>Patients and methods</title>
<sec>
<title/>
<sec>
<title>Subjects</title>
<p>In the present study, a total of 125 patients with NSCLC who underwent tumor resection surgery between April 2019 and January 2022 at North Sichuan Medical University affiliated Nanchong Central Hospital (Nanchong, China) were enrolled. The inclusion criteria were as follows: i) Patients diagnosed with NSCLC by pathological examination; ii) aged &#x2265;18 years; iii) received tumor resection surgery; and iv) followed the normal follow-up requirements. In addition, the exclusion criteria were as follows: i) Patients whose NSCLC was accompanied by other primary types of cancer; ii) suffering from hematological malignancies; iii) with needle or blood phobia; and iv) pregnant women or lactating mothers. Additionally, a total of 20 healthy individuals undergoing physical examination between February and March 2024 were enrolled as the control group. The recruitment criteria for individuals into the control group were as follows: i) Subjects without any abnormalities in recent physical examinations; ii) aged &#x003E;18 years; and iii) those who were willing to cooperate with blood collection. The exclusion criteria of patients with NSCLC were also applied to individuals in the healthy control group. The present study was approved by the Ethics Committee of North Sichuan Medical University affiliated Nanchong Central Hospital (approval no. 2024018; Nanchong, China), and most patients with NSCLC and the controls had provided written informed consent, while a waiver was obtained for certain patients with NSCLC who had not provided informed consent.</p>
</sec>
<sec>
<title>Data collection and sample detection</title>
<p>The clinical characteristics of patients with NSCLC, including demographic, and disease- and therapy-related data, were collected. The tumor-node-metastasis (TNM) stage was defined according to the guidelines provided by the International Association for the Study of Lung Cancer (<xref rid="b22-ol-30-2-15127" ref-type="bibr">22</xref>). Prior to treatment initiation, neoadjuvant therapy or tumor resection surgery, 2 ml peripheral blood (PB) was collected from all patients with NSCLC. In addition, PB from healthy controls was collected immediately after enrollment. For MALT1 detection, PB mononuclear cells (PBMCs) were separated from PB, and MALT1 levels were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. For qPCR, the thermocycling was as follows: 95&#x00B0;C for 60 sec, 1 cycle; 95&#x00B0;C for 15 sec and 61&#x00B0;C for 60 sec, 40 cycles. GAPDH was used as the internal reference and MALT1 levels were quantified using the 2<sup>&#x2212;&#x0394;&#x0394;Cq</sup> method (<xref rid="b23-ol-30-2-15127" ref-type="bibr">23</xref>). The primer sequences were as follows: MALT1 forward (F), 5&#x2032;-TCTTGGCTGGACAGTTTGTGA-3&#x2032; and reverse (R), 5&#x2032;-GCTCTCTGGGATGTCGCAA-3&#x2032;; GAPDH F, 5&#x2032;-TGACCACAGTCCATGCCATCAC-3&#x2032; and R, 5&#x2032;-GCCTGCTTCACCACCTTCTTGA-3&#x2032;. The corresponding kits used for RT-qPCR are listed in <xref rid="SD2-ol-30-2-15127" ref-type="supplementary-material">Table SI</xref> and the kits were used according to the manufacturer&#x0027;s instructions.</p>
</sec>
<sec>
<title>Grading of MALT1 levels</title>
<p>MALT1 expression levels in patients with NSCLC were divided into four different grades. The quartile (Q) values for each grade were as follows: i) Q1, MALT1 ranged from the minimum value, 0.690, to the 1st quartile value, 2.190 (Q1, 0.690&#x2013;2.190); ii) Q2, MALT1 ranged from the 1st quartile value to the 2nd quartile value, 3.600 (2.190&#x2013;3.600); iii) Q3, MALT1 ranged from the 2nd quartile value to the 3rd quartile value, 5.945 (Q3, 3.600&#x2013;5.945); and iv) Q4, MALT1 ranged from the 3rd quartile value to the maximum value, 12.770 (Q4, 5.945&#x2013;12.770).</p>
</sec>
<sec>
<title>Follow-up and evaluation</title>
<p>Routine follow-up was conducted, with a median follow-up time of 18.1 months (range, 2.8&#x2013;39.1 months). In the first year after surgery, follow-up was conducted once every 3 months and once every 3&#x2013;6 months thereafter. If the patients experienced disease recurrence, a follow-up was performed once every 2 months. During the follow-up, the disease progression status, death and the corresponding periods were recorded. The accumulating disease-free survival (DFS) and overall survival (OS) rates were calculated.</p>
</sec>
<sec>
<title>Bioinformatics</title>
<p>The association of MALT1 gene expression levels with TNM stage, DFS and OS in patients with NSCLC using publicly data was performed as well, which was based on the Gene Expression Profiling Interactive Analysis (GEPIA) database (<uri xlink:href="https://gepia.cancer-pku.cn/">http://gepia.cancer-pku.cn/</uri>). Correlation analysis of MALT1 gene expression with immune infiltrates in various types of cancer and NSCLC specifically using publicly available data was performed using the TIMER database (<uri xlink:href="https://timer.comp-genomics.org/">http://timer.comp-genomics.org/</uri>).</p>
</sec>
<sec>
<title>Statistical analyses</title>
<p>Data analyses were performed using SPSS (version 26.0; IBM Corp.). Categorical data were expressed as number (percentage), normally distributed continuous data were expressed as the mean &#x00B1; standard deviation and skewedly distributed continuous data were expressed as the median [interquartile range (IQR)]. To compare the clinical characteristics between different grades of MALT1, the Mann-Whitney U-test, &#x03C7;<sup>2</sup> test or Fisher&#x0027;s exact test was carried out. In addition, to compare accumulating DFS/OS rates between patients with NSCLC with different grades of MALT1, a log-rank test was performed. The results were displayed by Kaplan-Meier curves. Enter-method Cox regression models were used to identify the factors that were independently associated with DFS or OS. P&#x003C;0.05 was considered to indicate a statistically significant difference.</p>
</sec>
</sec>
</sec>
<sec sec-type="results">
<title>Results</title>
<sec>
<title/>
<sec>
<title>Characteristics of patients with NSCLC</title>
<p>A total of 125 patients with NSCLC were included in the present study. The mean age of the patients with NSCLC was 57.1&#x00B1;12.3 years. Among them, 27.2 and 72.8&#x0025; were &#x2265;65 and &#x003C;65 years old, respectively. A total of 54.4&#x0025; of patients were males and 45.6&#x0025; were females (<xref rid="tI-ol-30-2-15127" ref-type="table">Table I</xref>), while 61.6, 28.8 and 9.6&#x0025; of the patients were categorized as lung adenocarcinoma, lung squamous cell carcinoma and others, respectively. In addition, 36.0&#x0025; of the cases had poor differentiation, and 8.0, 8.8, 20.0, 39.2, 21.6 and 2.4&#x0025; of patients were of TNM stage of IA, IB, IIA, IIB, IIIA and IIIB, respectively. The mean age of the healthy control subjects was 55.5&#x00B1;5.2 years, consisting of 50&#x0025; females and 50&#x0025; males. Age (P=0.384) and sex (P=0.714) were not significantly different between the healthy controls and patients with NSCLC (<xref rid="SD2-ol-30-2-15127" ref-type="supplementary-material">Table SII</xref>).</p>
</sec>
<sec>
<title>MALT1 is aberrantly expressed in the blood and is associated with the clinical characteristics of patients with NSCLC</title>
<p>The blood MALT1 mRNA expression levels were quantified in the 20 healthy subjects and patients with NSCLC. The relative expression levels of MALT1 mRNA were increased in the blood samples of patients with NSCLC (median, 3.60; IQR, 2.19&#x2013;5.95) compared with the healthy controls (median, 1.06; IQR, 0.66&#x2013;2.29; P&#x003C;0.001; <xref rid="f1-ol-30-2-15127" ref-type="fig">Fig. 1</xref>), suggesting MALT1 was aberrantly expressed in the blood of patients with NSCLC. Subsequently, to analyze the association between blood MALT1 levels and clinical features, treatment options and prognosis in patients with NSCLC, the mRNA expression levels of MALT1 were divided into four groups, according to the quartiles (Q1, Q2, Q3 and Q4). The results demonstrated that the blood MALT1 quartile was markedly positively associated with the N (P=0.026) and TNM (P=0.036) stages in patients with NSCLC. Additionally, MALT1 expression levels displayed a tendency to be positively associated with poor differentiation (P=0.091) and T stage (P=0.058; <xref rid="tI-ol-30-2-15127" ref-type="table">Table I</xref>), but this did not reach statistical significance. By contrast, the blood MALT1 quartile was not associated with other clinical characteristics or with neoadjuvant therapy, surgical type or adjuvant therapy.</p>
</sec>
<sec>
<title>Prognostic value of blood MALT1 levels in patients with NSCLC</title>
<p>The blood MALT1 quartile was associated with shorter DFS (P=0.009), with 3-year accumulating DFS rates of 92.9, 68.8, 41.4 and 28.2&#x0025; in patients with MALT1 levels at Q1, Q2, Q3 and Q4, respectively (<xref rid="f2-ol-30-2-15127" ref-type="fig">Fig. 2A</xref>). However, the blood MALT1 quartile only showed a tendency to be associated with poor OS in these patients (P=0.118), but it did not reach statistical significance; 3-year accumulating OS rates of 100.0, 84.4, 65.7 and 44.5&#x0025; were recorded in patients with MALT1 levels at Q1, Q2, Q3 and Q4, respectively (<xref rid="f2-ol-30-2-15127" ref-type="fig">Fig. 2B</xref>). The aforementioned data suggested that blood MALT1expression levels may potentially predict DFS; however, they lacked efficiency in OS estimations of patients with NSCLC. Furthermore, multivariate Cox analysis was performed to identify the factors that could affect DFS and OS in patients with NSCLC. Increased MALT1 quartile [P=0.016; hazard ratio (HR), 1.712], age (P=0.026; HR, 1.043) and TNM stage (P=0.001; HR, 10.734) had a negative impact on DFS independently, while adjuvant tyrosine kinase inhibitor therapy (P=0.038; HR, 0.244) was independently associated with satisfied DFS (<xref rid="f3-ol-30-2-15127" ref-type="fig">Fig. 3</xref>). In terms of OS, a higher MALT1 quartile (P=0.293; HR, 1.477) was not significantly associated with OS. However, a higher TNM stage (P=0.009; HR, 21.113) was significantly associated with lower OS rates (<xref rid="f4-ol-30-2-15127" ref-type="fig">Fig. 4</xref>).</p>
</sec>
<sec>
<title>Bioinformatic analyses based on public database</title>
<p>GEPIA is a developed interactive web server for analyzing the RNA sequencing expression data from the The Cancer Genome Atlas and the Genotype-Tissue Expression projects, using a standard processing pipeline (<xref rid="b24-ol-30-2-15127" ref-type="bibr">24</xref>). With the use of GEPIA, it was observed that MALT1 was not related to TNM stage, DFS or OS in patients with lung adenocarcinoma (<xref rid="SD1-ol-30-2-15127" ref-type="supplementary-material">Fig. S1A</xref>), nor in patients with lung squamous cell carcinoma (<xref rid="SD1-ol-30-2-15127" ref-type="supplementary-material">Fig. S1B</xref>). MALT1 showed a notable association with DFS in lung squamous cell carcinoma but this was not of statistical significance.</p>
<p>The TIMER database is a comprehensive resource for the systematic analysis of immune infiltrates across diverse types of cancer (<xref rid="b25-ol-30-2-15127" ref-type="bibr">25</xref>). The TIMER database was used for immune analysis and demonstrated that MALT1 expression levels were correlated with macrophages and CD8<sup>&#x002B;</sup> T cells in various types of cancer (<xref rid="SD1-ol-30-2-15127" ref-type="supplementary-material">Fig. S1C and D</xref>). Regarding NSCLC, MALT1 was closely correlated with macrophages (particularly the M1 type) and CD8<sup>&#x002B;</sup> T cells in lung adenocarcinoma, but the correlation was lower in lung squamous cell carcinoma.</p>
</sec>
</sec>
</sec>
<sec sec-type="discussion">
<title>Discussion</title>
<p>It has been suggested that MATL1 is a significant carcinogenetic factor that promotes the initiation and progression of several types of cancer (<xref rid="b11-ol-30-2-15127" ref-type="bibr">11</xref>&#x2013;<xref rid="b21-ol-30-2-15127" ref-type="bibr">21</xref>). More specifically, the role of MALT1 inhibitor as a candidate treatment option for hepatocellular carcinoma, colorectal cancer, chronic lymphocytic leukemia and glioblastoma both <italic>in vivo</italic> and <italic>in vitro</italic>, has been recently investigated (<xref rid="b13-ol-30-2-15127" ref-type="bibr">13</xref>,<xref rid="b26-ol-30-2-15127" ref-type="bibr">26</xref>&#x2013;<xref rid="b28-ol-30-2-15127" ref-type="bibr">28</xref>). Due to these functions, MALT1 has attracted increasing attention as a biomarker in different types of cancer. Previous studies demonstrated that MALT1 was upregulated in colorectal cancer, melanoma and lymphomas (<xref rid="b16-ol-30-2-15127" ref-type="bibr">16</xref>&#x2013;<xref rid="b18-ol-30-2-15127" ref-type="bibr">18</xref>). However, the aforementioned studies detected the expression levels of MALT1 in cancerous tissues. Therefore, data on the expression levels of MALT1 in blood samples are lacking. The present study demonstrated that MALT1 was upregulated in blood samples from patients with NSCLC compared with the control group (&#x007E;3.4-fold). This finding could be due to the possible promoting role of MALT1 in lung cancer (<xref rid="b19-ol-30-2-15127" ref-type="bibr">19</xref>,<xref rid="b20-ol-30-2-15127" ref-type="bibr">20</xref>) and its effects on CD8<sup>&#x002B;</sup> T-cell functions, immune escape and anticancer immunity (<xref rid="b29-ol-30-2-15127" ref-type="bibr">29</xref>&#x2013;<xref rid="b31-ol-30-2-15127" ref-type="bibr">31</xref>).</p>
<p>Subsequently, the present study also demonstrated that blood MALT1 expression levels were positively associated with N and TNM stages in patients with NSCLC, and showed a notable positive association with poor differentiation and T stage, thus supporting the possible role of MALT1 in predicting tumor progression or disease burden in patients with NSCLC. These findings could be for the following reasons: i) Previous studies demonstrated that MALT1 could directly activate NF-&#x03BA;B to promote NSCLC progression, while blood MALT1 levels could also reflect the expression levels of MALT1 in tumor tissues, to a certain extent (<xref rid="b32-ol-30-2-15127" ref-type="bibr">32</xref>,<xref rid="b33-ol-30-2-15127" ref-type="bibr">33</xref>); ii) in addition to the NF-&#x03BA;B signaling pathway, bioinformatics analysis in the Kyoto Encyclopedia of Genes and Genomes predicted that MALT1 could also regulate the C-type lectin, T-cell and B-cell receptor signaling pathways, thus promoting NSCLC progression (<xref rid="b34-ol-30-2-15127" ref-type="bibr">34</xref>,<xref rid="b35-ol-30-2-15127" ref-type="bibr">35</xref>); and ii) other studies also suggested that the T-cell receptor signaling pathway, a notable downstream pathway of MALT1, could affect tumor immunity and immune escape to promote NSCLC progression (<xref rid="b36-ol-30-2-15127" ref-type="bibr">36</xref>&#x2013;<xref rid="b38-ol-30-2-15127" ref-type="bibr">38</xref>).</p>
<p>The present study also suggested that blood MALT1 levels may predict the prognosis of patients with NSCLC. Kaplan-Meier curves predicted that the expression levels of MALT1 in the blood of patients with NSCLC were associated with a shorter DFS, while they showed a notable association with worse OS. Further adjustment by multivariate Cox analysis demonstrated that the expression levels of MALT1 could independently predict unsatisfied DFS. The prognostic value of blood MALT1 levels could be due to the following: i) Correlation analysis revealed that MALT1 was associated with advanced tumor conditions, such as N and TNM stages, thus possibly affecting the prognosis of patients with NSCLC; and ii) a large proportion of patients with NSCLC were treated with adjuvant therapies. It has been reported that MALT1 regulates the sensitivity of patients to adjuvant therapies (<xref rid="b19-ol-30-2-15127" ref-type="bibr">19</xref>,<xref rid="b21-ol-30-2-15127" ref-type="bibr">21</xref>,<xref rid="b39-ol-30-2-15127" ref-type="bibr">39</xref>). Therefore, the aforementioned findings could affect the prognosis of patients with NSCLC. Furthermore, the lack of significance regarding the association between MALT1 levels and OS could be due to the fact that OS could be affected by several factors, such as treatment after tumor recurrence, comorbidity and supportive treatment. These factors may weaken the predictive value of MALT1 regarding the prognosis of patients with NSCLC. Furthermore, GEPIA database analysis revealed that MALT1 was not correlated with DFS or OS in lung cancer and the difference between the aforementioned GEPIA data and the present findings may have been due to the fact that tumor tissue was used in GEPIA, while blood samples were used in the present study.</p>
<p>However, the present study had certain limitations. First, the present study only included surgical patients with NSCLC to avoid interference, since the prognosis of advanced cases was far from surgical ones, which limited the generalizability of the study findings. More patients with different types of lung cancer would have been needed to be included to obtain more comprehensive conclusions. Second, the sample size of the present study was relatively small, which may limit the reliability and generalizability of the results. Therefore, more large population-based validation studies are needed to verify the results of the present study. Third, the follow-up time of the present study was relatively short and it was difficult to assess the correlation between blood MALT1 and long-term prognosis. Therefore, longer follow-up studies are needed to verify the long-term prognostic value of blood MALT1 expression levels. Finally, no investigation into the mechanistic relationship between blood MALT1 levels and the development and prognosis of NSCLC was performed, which could be further evaluated in future studies.</p>
<p>In conclusion, the results of the present study suggested that blood MALT1 levels could potentially reflect the stage of lymph node metastasis and predict DFS in patients with NSCLC. This suggests the potential of blood MALT1 to be a prognostic biomarker in patients with NSCLC, which could help facilitate personalized treatment via early identifying prognostic risk stratification. However, future large-scale studies with a longer follow-up duration are needed to further validate the results of the present study.</p>
</sec>
<sec sec-type="supplementary-material">
<title>Supplementary Material</title>
<supplementary-material id="SD1-ol-30-2-15127" content-type="local-data">
<caption>
<title>Supporting Data</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD2-ol-30-2-15127" content-type="local-data">
<caption>
<title>Supporting Data</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data2.pdf"/>
</supplementary-material>
</sec>
</body>
<back>
<ack>
<title>Acknowledgements</title>
<p>Not applicable.</p>
</ack>
<sec sec-type="data-availability">
<title>Availability of data and materials</title>
<p>The data generated in the present study may be requested from the corresponding author.</p>
</sec>
<sec>
<title>Authors&#x0027; contributions</title>
<p>XZ contributed to the study conception and design. Data collection and analysis were performed by FZ and BW. XP was responsible for the interpretation of data for the present study. XZ and FZ confirm the authenticity of all the raw data. All authors contributed to drafting of article and revising it critically for important intellectual content. All authors read and approved the final manuscript.</p>
</sec>
<sec>
<title>Ethics approval and consent to participate</title>
<p>The Ethics Committee of North Sichuan Medical University (Nanchong, China) approved the present study (approval no. 2024018). Most NSCLC patients and the controls had provided written informed consent, while a waiver was obtained for certain patients with NSCLC who had not provided informed consent.</p>
</sec>
<sec>
<title>Patient consent for publication</title>
<p>Not applicable.</p>
</sec>
<sec sec-type="COI-statement">
<title>Competing interests</title>
<p>The authors declare that they have no competing interests.</p>
</sec>
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<floats-group>
<fig id="f1-ol-30-2-15127" position="float">
<label>Figure 1.</label>
<caption><p>Comparison of blood MALT1 mRNA expression levels between patients with NSCLC and health controls. The values printed in the figure are expressed as the median (interquartile range). NSCLC, non-small cell lung cancer; MALT, mucosa-associated lymphoid tissue lymphoma translocation protein-1.</p></caption>
<graphic xlink:href="ol-30-02-15127-g00.tif"/>
</fig>
<fig id="f2-ol-30-2-15127" position="float">
<label>Figure 2.</label>
<caption><p>Correlation of MALT1 quartiles with prognosis of patients with NSCLC. Correlation of MALT1 quartiles with (A) DFS and (B) OS reflected by Kaplan-Meier curves in patients with NSCLC. NSCLC, non-small cell lung cancer; MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein-1; DFS, disease-free survival; OS, overall survival.</p></caption>
<graphic xlink:href="ol-30-02-15127-g01.tif"/>
</fig>
<fig id="f3-ol-30-2-15127" position="float">
<label>Figure 3.</label>
<caption><p>Multivariate Cox analysis for DFS. MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein-1; DFS, disease-free survival; HR, hazard ratio; TNM, tumor-node-metastasis; TKI, tyrosine kinase inhibitor; ICI, immune checkpoint inhibitor.</p></caption>
<graphic xlink:href="ol-30-02-15127-g02.tif"/>
</fig>
<fig id="f4-ol-30-2-15127" position="float">
<label>Figure 4.</label>
<caption><p>Multivariate Cox analysis for OS. OS, overall survival; MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein-1; HR, hazard ratio; TNM, tumor-node-metastasis; TKI, tyrosine kinase inhibitor; ICI, immune checkpoint inhibitor.</p></caption>
<graphic xlink:href="ol-30-02-15127-g03.tif"/>
</fig>
<table-wrap id="tI-ol-30-2-15127" position="float">
<label>Table I.</label>
<caption><p>Clinical characteristics of patients with NSCLC.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="bottom">Characteristics</th>
<th align="center" valign="bottom">Total (n=125)</th>
<th align="center" valign="bottom">Q1-MALT1 (n=31)</th>
<th align="center" valign="bottom">Q2-MALT1 (n=32)</th>
<th align="center" valign="bottom">Q3-MALT1 (n=31)</th>
<th align="center" valign="bottom">Q4-MALT1 (n=31)</th>
<th align="center" valign="bottom">P-value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Age, years</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.245</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;&#x003C;65</td>
<td align="center" valign="top">91 (72.8)</td>
<td align="center" valign="top">24 (26.4)</td>
<td align="center" valign="top">21 (23.1)</td>
<td align="center" valign="top">26 (28.6)</td>
<td align="center" valign="top">20 (22.0)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;&#x2265;65</td>
<td align="center" valign="top">34 (27.2)</td>
<td align="center" valign="top">7 (20.6)</td>
<td align="center" valign="top">11 (32.4)</td>
<td align="center" valign="top">5 (14.7)</td>
<td align="center" valign="top">11 (32.4)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Sex</td>
<td/>
<td align="center" valign="top"/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.793</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Female</td>
<td align="center" valign="top">57 (45.6)</td>
<td align="center" valign="top">15 (26.3)</td>
<td align="center" valign="top">13 (22.8)</td>
<td align="center" valign="top">16 (28.1)</td>
<td align="center" valign="top">13 (22.8)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Male</td>
<td align="center" valign="top">68 (54.4)</td>
<td align="center" valign="top">16 (23.5)</td>
<td align="center" valign="top">19 (27.9)</td>
<td align="center" valign="top">15 (22.1)</td>
<td align="center" valign="top">18 (26.5)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Smoking status</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.463</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Never smoked</td>
<td align="center" valign="top">84 (67.2)</td>
<td align="center" valign="top">24 (28.6)</td>
<td align="center" valign="top">22 (26.2)</td>
<td align="center" valign="top">19 (22.6)</td>
<td align="center" valign="top">19 (22.6)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Former smoker</td>
<td align="center" valign="top">15 (12.0)</td>
<td align="center" valign="top">3 (20.0)</td>
<td align="center" valign="top">5 (33.3)</td>
<td align="center" valign="top">5 (33.3)</td>
<td align="center" valign="top">2 (13.3)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Current smoker</td>
<td align="center" valign="top">26 (20.8)</td>
<td align="center" valign="top">4 (15.4)</td>
<td align="center" valign="top">5 (19.2)</td>
<td align="center" valign="top">7 (26.9)</td>
<td align="center" valign="top">10 (38.5)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Histological type</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.263</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Lung adenocarcinoma</td>
<td align="center" valign="top">77 (61.6)</td>
<td align="center" valign="top">16 (20.8)</td>
<td align="center" valign="top">17 (22.1)</td>
<td align="center" valign="top">21 (27.3)</td>
<td align="center" valign="top">23 (29.9)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Lung squamous cell carcinoma</td>
<td align="center" valign="top">36 (28.8)</td>
<td align="center" valign="top">9 (25.0)</td>
<td align="center" valign="top">13 (36.1)</td>
<td align="center" valign="top">8 (22.2)</td>
<td align="center" valign="top">6 (16.7)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Other</td>
<td align="center" valign="top">12 (9.6)</td>
<td align="center" valign="top">6 (50.0)</td>
<td align="center" valign="top">2 (16.7)</td>
<td align="center" valign="top">2 (16.7)</td>
<td align="center" valign="top">2 (16.7)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Poor differentiation</td>
<td align="center" valign="top">45 (36.0)</td>
<td align="center" valign="top">9 (20.0</td>
<td align="center" valign="top">9 (20.0)</td>
<td align="center" valign="top">10 (22.2)</td>
<td align="center" valign="top">17 (37.8)</td>
<td align="center" valign="top">0.091</td>
</tr>
<tr>
<td align="left" valign="top">T stage</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.058</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;1</td>
<td align="center" valign="top">14 (11.2)</td>
<td align="center" valign="top">6 (42.9)</td>
<td align="center" valign="top">4 (28.6)</td>
<td align="center" valign="top">1 (7.1)</td>
<td align="center" valign="top">3 (21.4)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;2</td>
<td align="center" valign="top">68 (54.4)</td>
<td align="center" valign="top">19 (27.9)</td>
<td align="center" valign="top">19 (27.9)</td>
<td align="center" valign="top">20 (29.4)</td>
<td align="center" valign="top">10 (14.7)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;3</td>
<td align="center" valign="top">34 (27.2)</td>
<td align="center" valign="top">5 (14.7)</td>
<td align="center" valign="top">6 (17.6)</td>
<td align="center" valign="top">8 (23.5)</td>
<td align="center" valign="top">15 (44.1)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;4</td>
<td align="center" valign="top">9 (7.2)</td>
<td align="center" valign="top">1 (11.1)</td>
<td align="center" valign="top">3 (33.3)</td>
<td align="center" valign="top">2 (22.2)</td>
<td align="center" valign="top">3 (33.3)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">N stage</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.026</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;0</td>
<td align="center" valign="top">66 (52.8)</td>
<td align="center" valign="top">21 (31.8)</td>
<td align="center" valign="top">14 (21.2)</td>
<td align="center" valign="top">14 (21.2)</td>
<td align="center" valign="top">17 (25.8)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;1</td>
<td align="center" valign="top">54 (43.2)</td>
<td align="center" valign="top">9 (16.7)</td>
<td align="center" valign="top">18 (33.3)</td>
<td align="center" valign="top">17 (31.5)</td>
<td align="center" valign="top">10 (18.5)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;2</td>
<td align="center" valign="top">5 (4.0)</td>
<td align="center" valign="top">1 (20.0)</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">4 (80.0)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">M stage</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;0</td>
<td align="center" valign="top">125 (100.0)</td>
<td align="center" valign="top">31 (24.8)</td>
<td align="center" valign="top">32 (25.6)</td>
<td align="center" valign="top">31 (24.8)</td>
<td align="center" valign="top">31 (24.8)</td>
<td align="center" valign="top">(&#x2212;)</td>
</tr>
<tr>
<td align="left" valign="top">TNM detailed stage</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.036</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;IA</td>
<td align="center" valign="top">10 (8.0)</td>
<td align="center" valign="top">4 (40.0)</td>
<td align="center" valign="top">3 (30.0)</td>
<td align="center" valign="top">1 (10.0)</td>
<td align="center" valign="top">2 (20.0)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;IB</td>
<td align="center" valign="top">11 (8.8)</td>
<td align="center" valign="top">2 (18.2)</td>
<td align="center" valign="top">3 (27.3)</td>
<td align="center" valign="top">3 (27.3)</td>
<td align="center" valign="top">3 (27.3)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;IIA</td>
<td align="center" valign="top">25 (20.0)</td>
<td align="center" valign="top">13 (52.0)</td>
<td align="center" valign="top">5 (20.0)</td>
<td align="center" valign="top">4 (16.0)</td>
<td align="center" valign="top">3 (12.0)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;IIB</td>
<td align="center" valign="top">49 (39.2)</td>
<td align="center" valign="top">7 (14.3)</td>
<td align="center" valign="top">14 (28.6)</td>
<td align="center" valign="top">18 (36.7)</td>
<td align="center" valign="top">10 (20.40</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;IIIA</td>
<td align="center" valign="top">27(21.6)</td>
<td align="center" valign="top">5 (18.5)</td>
<td align="center" valign="top">7 (25.9)</td>
<td align="center" valign="top">5 (18.5)</td>
<td align="center" valign="top">10 (37.0)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;IIIB</td>
<td align="center" valign="top">3 (2.4)</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">3 (100.0)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Neoadjuvant chemotherapy</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.188</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;No</td>
<td align="center" valign="top">102 (81.6)</td>
<td align="center" valign="top">27 (26.5)</td>
<td align="center" valign="top">25 (24.5)</td>
<td align="center" valign="top">28 (27.5)</td>
<td align="center" valign="top">22 (21.6)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Yes</td>
<td align="center" valign="top">23 (18.4)</td>
<td align="center" valign="top">4 (17.4)</td>
<td align="center" valign="top">7 (30.4)</td>
<td align="center" valign="top">3 (13.0)</td>
<td align="center" valign="top">9 (39.1)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Neoadjuvant TKI</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.754</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;No</td>
<td align="center" valign="top">121 (96.8)</td>
<td align="center" valign="top">31 (25.6)</td>
<td align="center" valign="top">31 (25.6)</td>
<td align="center" valign="top">30 (24.8)</td>
<td align="center" valign="top">29 (24.0)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Yes</td>
<td align="center" valign="top">4 (3.2)</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">1 (25.0)</td>
<td align="center" valign="top">1 (25.0)</td>
<td align="center" valign="top">2 (50.0)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Neoadjuvant ICI</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.571</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;No</td>
<td align="center" valign="top">120 (96.0)</td>
<td align="center" valign="top">31 (25.8)</td>
<td align="center" valign="top">31 (25.8)</td>
<td align="center" valign="top">29 (24.2)</td>
<td align="center" valign="top">29 (24.2)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Yes</td>
<td align="center" valign="top">5 (4.0)</td>
<td align="center" valign="top">0 (0.0)</td>
<td align="center" valign="top">1 (20.0)</td>
<td align="center" valign="top">2 (40.0)</td>
<td align="center" valign="top">2 (40.0)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Surgical type</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.817</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Thoracoscopic surgery</td>
<td align="center" valign="top">19 (15.2)</td>
<td align="center" valign="top">5 (26.3)</td>
<td align="center" valign="top">6 (31.6)</td>
<td align="center" valign="top">5 (26.3)</td>
<td align="center" valign="top">3 (15.8)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Thoracotomy</td>
<td align="center" valign="top">106 (84.8)</td>
<td align="center" valign="top">26 (24.5)</td>
<td align="center" valign="top">26 (24.5)</td>
<td align="center" valign="top">26 (24.5)</td>
<td align="center" valign="top">28 (26.4)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Adjuvant chemotherapy</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.157</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;No</td>
<td align="center" valign="top">42 (33.6)</td>
<td align="center" valign="top">15 (35.7)</td>
<td align="center" valign="top">9 (21.4)</td>
<td align="center" valign="top">11 (26.2)</td>
<td align="center" valign="top">7 (16.7)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Yes</td>
<td align="center" valign="top">83 (66.4)</td>
<td align="center" valign="top">16 (19.3)</td>
<td align="center" valign="top">23 (27.7)</td>
<td align="center" valign="top">20 (24.1)</td>
<td align="center" valign="top">24 (28.9)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Adjuvant TKI</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.406</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;No</td>
<td align="center" valign="top">102 (81.6)</td>
<td align="center" valign="top">25 (24.5)</td>
<td align="center" valign="top">29 (28.4)</td>
<td align="center" valign="top">23 (22.5)</td>
<td align="center" valign="top">25 (24.5)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Yes</td>
<td align="center" valign="top">23 (18.4)</td>
<td align="center" valign="top">6 (26.1)</td>
<td align="center" valign="top">3 (13.0)</td>
<td align="center" valign="top">8 (34.8)</td>
<td align="center" valign="top">6 (26.1)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Adjuvant ICI</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="center" valign="top">0.737</td>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;No</td>
<td align="center" valign="top">110 (88.0)</td>
<td align="center" valign="top">29 (26.4)</td>
<td align="center" valign="top">28 (25.5)</td>
<td align="center" valign="top">26 (23.6)</td>
<td align="center" valign="top">27 (24.5)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">&#x00A0;&#x00A0;Yes</td>
<td align="center" valign="top">15 (12.0)</td>
<td align="center" valign="top">2 (13.3)</td>
<td align="center" valign="top">4 (26.7)</td>
<td align="center" valign="top">5 (33.3)</td>
<td align="center" valign="top">4 (26.7)</td>
<td/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn1-ol-30-2-15127"><p>The P-value reflects the association between different grades of MALT1 and the characteristics of patients with NSCLC. NSCLC, non-small cell lung cancer; MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein 1; Q1, first quartile; Q2, second quartile; Q3, third quartile; Q4, fourth quartile; TNM, tumor-mode-metastasis; TKI, tyrosine kinase inhibitor; ICI, immune checkpoint inhibitor. (&#x2212;): Since all patients were at M0 stage, therefore the analysis cannot be performed, so (&#x2212;) was presented.</p></fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</article>
