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Amplification of heterogeneous nuclear ribonucleoprotein A/B aids in immune infiltration regulation and breast cancer tumorigenesis

  • Authors:
    • Jiachao Xu
    • Qian Han
    • Libin Chen
    • Min Yang
    • Jun Huang
    • Shanhong Lin
    • Shengmin Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Ultrasound Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315500, P.R. China, Department of Neurosurgery, Shaoxing People's Hospital, Shaoxing, Zhejiang 312300, P.R. China
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 198
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    Published online on: May 27, 2026
       https://doi.org/10.3892/etm.2026.13193
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Abstract

Breast carcinoma ranks among the most prevalent malignant tumors affecting women worldwide. The discovery of biomarkers is important in the diagnosis of breast cancer and the prediction of clinical outcomes in afflicted patients. Heterogeneous nuclear ribonucleoprotein (HNRNP)‑AB belongs to the extensive HNRNP superfamily; however, its exact role in the progression of breast carcinoma has not yet been fully clarified. The present study drew upon breast cancer sample datasets retrieved from The Cancer Genome Atlas and Human Protein Atlas databases to examine the expression patterns and prognosis‑associated data of HNRNPAB in clinical specimens. Reverse transcription‑quantitative PCR was employed to validate the efficiency of HNRNPAB knockdown in breast cancer cell lines. Transwell assays and Cell Counting Kit‑8 tests further demonstrated alterations in migratory, invasive and proliferative capacities following small interfering RNA‑mediated HNRNPAB knockdown. Bioinformatics was utilized to investigate numerous aspects of HNRNPAB in cancerous tissues, including its mRNA expression profile, prognostic value, signaling pathway remodeling, interaction with cancer stem cells and regulatory effects on the tumor immune microenvironment, as well as immunotherapeutic responses. Compared with normal breast tissues, HNRNPAB exhibited elevated expression in breast cancer tissues, upregulation that appeared to be associated with overall survival outcomes, sex characteristics, lymph node metastasis staging and adverse prognostic profiles in patients. Functionally, HNRNPAB depletion was found to suppress the proliferative activity, migratory potential and invasive capabilities of breast cancer cells. Mechanistically, bioinformatics analyses indicated that high HNRNPAB expression was associated with the tumor immune infiltration status in affected individuals. In summary, the present study determined that HNRNPAB exerted a key regulatory effect on the development and progression of breast cancer and therefore its upregulation holds promise as a diagnostic and prognostic marker. In addition, HNRNPAB serves a notable role in cancer immunotherapy, supporting its potential as a novel therapeutic candidate for the early detection and prognostic evaluation of breast cancer.
View Figures

Figure 1

Expression of HNRNPAB and its
association with clinical prognosis of patients with breast cancer.
(A) Differential expression of HNRNPAB in different cancer types
based on pan-cancer analysis. (B) Expression of HNRNPAB in BRCA
tissue samples in TCGA database is higher than compared with
paracancerous tissues of breast cancer. HNRNPAB
immunohistochemistry images obtained from the Human Protein Atlas
database show that the expression level of HNRNPAB protein in (C)
breast cancer tissues is higher compared with that in (D)
paracancerous tissues of breast cancer. (E) The influence of
HNRNPAB expression on the prognosis of patients with breast cancer
analyzed by the Kaplan-Meier method. Box plots describing the
expression analysis of HNRNPAB according to (F) stage, (G) lymph
node metastasis, (H) age and (I) breast cancer histology. (J)
Scatter plot showing the correlation between HNRNPAB expression and
ploidy in various tumors, with red indicating a positive
correlation and blue indicating a negative correlation. HNRNPAB,
heterogeneous nuclear ribonucleoprotein A/B; TPM, transcripts per
million; HR, hazard ratio; TCGA, The Cancer Genome Atlas; IDC,
invasive ductal carcinoma; ILC, invasive lobular carcinoma; INOS,
infiltrating carcinoma not otherwise specified.
*P<0.05, **P<0.01 and
****P<0.0001.

Figure 2

Role of HNRNPAB in breast cancer
cells. (A) Reverse transcription-quantitative PCR was used to
detect the expression level of mRNA in stably knocked-down cells of
HNRNPAB. GAPDH was used as the internal reference. (B) The
proliferation capacity of MDA-MB-231 breast cancer cells
transfected with HNRNPAB siRNA in CCK8 is lower compared with that
of the MDA-MB-231 siRNA blank group. siRNA transfection into
MDA-MB-231 breast cancer cells to reduce the expression level of
HNRNPAB. Transwell experiment showing that reducing the expression
of HNRNPAB can significantly inhibit the (C) migration and (D)
invasion ability of cancer cells. ***P<0.001.
HNRNPAB, heterogeneous nuclear ribonucleoprotein A/B; siRNA, small
interfering RNA; CCK-8, Cell Counting Kit-8; NC, negative
control.

Figure 3

Genetic alteration landscape of
HNRNPAB. Schematic diagrams depicting the (A) type and (B)
proportion of genetic alterations of HNRNPAB in patients with
breast cancer and breast cancer subclasses, using the cBioportal
database. (C) Oncoplot showing the somatic landscape of breast
tumor cohort. Genes are ordered by their mutation frequencies and
samples are ordered by expression of HNRNPAB, as indicated by the
annotation bar (bottom). Side bar plot shows the
-log10-transformed q-values, as estimated using
MutSigCV. Waterfall plot showing mutation information for each gene
for each sample. Color annotation of various cancer types are shown
at the bottom. The barplot above the legend shows the mutation
burden. (D) Stacked bar graph showing the top 10 mutated genes. (E
and F) Cohort summary plot showing the distribution of variants
according to (E) SNV class and (F) variant classification. HNRNPAB,
heterogeneous nuclear ribonucleoprotein A/B; SNV, single nucleotide
variant; GISTIC, Genomic Identification of Significant Targets in
Cancer; CNA, copy number alteration; NOS, not otherwise specified;
TMB, tumor mutational burden.

Figure 4

Enrichment analysis of differentially
expressed genes in heterogeneous nuclear ribonucleoprotein A/B. (A)
GSEA analysis based on HALLMARK analysis. (B) GSEA analysis based
on Kyoto Encyclopedia of Genes and Genomes analysis. (C) GSEA
analysis based on REACTEMO analysis. GSEA, Gene Set Enrichment
Analysis; ES, Enrichment Score; NP, nominal P-value.

Figure 5

Tumor microenvironment score and
immune cell infiltration. (A) The StromalScore, ImmuneScore and
ESTIMATEScore of the low expression group are significantly higher
compared with the high expression group. (B) Heat map displaying
the correlation between HNRNPAB expression and immune cell
infiltration in patients with breast cancer. The square above each
cell type is divided into two triangles. The color of the top left
triangle represents the correlation, where red indicates a positive
correlation and blue indicates a negative correlation. The color of
the bottom right triangle represents statistical significance, with
lighter colors indicating greater statistical significance. (C) In
breast cancer, HNRNPAB is shown to be significantly correlated with
11 immune checkpoint genes (blue represents a negative correlation
and red represents a positive correlation). (D) The Immune
Phenotype Score of the low expression group is higher compared with
the high expression group. *P<0.05 and
****P<0.01. HNRNPAB, heterogeneous nuclear
ribonucleoprotein A/B; TCGA, The Cancer Genome Atlas.

Figure 6

Association between HNRNPAB and
cancer stem cells. (A) Lollipop plot depicting the correlation
between HNRNPAB and tumor stemness in pan-cancer. The x-axis
represents different types of tumors, while the y-axis illustrates
the correlation between HNRNPAB expression and RNA stemness scores.
Correlation scatter plots illustrating the association between
HNRNPAB expression and (B) SOX2, (C) ITGB1 and (D) EPCAM in breast
cancer. A value of 0 denotes a positive correlation, while a value
of r<0 indicates a negative correlation. P<0.05 was
considered to indicate a statistically significant difference.
HNRNPAB, heterogeneous nuclear ribonucleoprotein A/B; ITGB1,
integrin subunit β-1; EPCAM, epithelial cell adhesion molecule.
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Copy and paste a formatted citation
Spandidos Publications style
Xu J, Han Q, Chen L, Yang M, Huang J, Lin S and Zhang S: Amplification of heterogeneous nuclear ribonucleoprotein A/B aids in immune infiltration regulation and breast cancer tumorigenesis. Exp Ther Med 32: 198, 2026.
APA
Xu, J., Han, Q., Chen, L., Yang, M., Huang, J., Lin, S., & Zhang, S. (2026). Amplification of heterogeneous nuclear ribonucleoprotein A/B aids in immune infiltration regulation and breast cancer tumorigenesis. Experimental and Therapeutic Medicine, 32, 198. https://doi.org/10.3892/etm.2026.13193
MLA
Xu, J., Han, Q., Chen, L., Yang, M., Huang, J., Lin, S., Zhang, S."Amplification of heterogeneous nuclear ribonucleoprotein A/B aids in immune infiltration regulation and breast cancer tumorigenesis". Experimental and Therapeutic Medicine 32.1 (2026): 198.
Chicago
Xu, J., Han, Q., Chen, L., Yang, M., Huang, J., Lin, S., Zhang, S."Amplification of heterogeneous nuclear ribonucleoprotein A/B aids in immune infiltration regulation and breast cancer tumorigenesis". Experimental and Therapeutic Medicine 32, no. 1 (2026): 198. https://doi.org/10.3892/etm.2026.13193
Copy and paste a formatted citation
x
Spandidos Publications style
Xu J, Han Q, Chen L, Yang M, Huang J, Lin S and Zhang S: Amplification of heterogeneous nuclear ribonucleoprotein A/B aids in immune infiltration regulation and breast cancer tumorigenesis. Exp Ther Med 32: 198, 2026.
APA
Xu, J., Han, Q., Chen, L., Yang, M., Huang, J., Lin, S., & Zhang, S. (2026). Amplification of heterogeneous nuclear ribonucleoprotein A/B aids in immune infiltration regulation and breast cancer tumorigenesis. Experimental and Therapeutic Medicine, 32, 198. https://doi.org/10.3892/etm.2026.13193
MLA
Xu, J., Han, Q., Chen, L., Yang, M., Huang, J., Lin, S., Zhang, S."Amplification of heterogeneous nuclear ribonucleoprotein A/B aids in immune infiltration regulation and breast cancer tumorigenesis". Experimental and Therapeutic Medicine 32.1 (2026): 198.
Chicago
Xu, J., Han, Q., Chen, L., Yang, M., Huang, J., Lin, S., Zhang, S."Amplification of heterogeneous nuclear ribonucleoprotein A/B aids in immune infiltration regulation and breast cancer tumorigenesis". Experimental and Therapeutic Medicine 32, no. 1 (2026): 198. https://doi.org/10.3892/etm.2026.13193
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