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Article Open Access

BUD23 is associated with malignancy and correlates with immune infiltration in NSCLC

  • Authors:
    • Yonghuang Tan
    • Jun Ma
    • Jiangli Zhou
    • Jianjun Lu
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat‑sen University, Guangzhou, Guangdong 510006, P.R. China
    Copyright: © Tan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 252
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    Published online on: April 20, 2026
       https://doi.org/10.3892/ol.2026.15608
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Abstract

Lung cancer remains the primary cause of cancer‑related mortality worldwide. BUD23, also known as Williams‑Beuren syndrome critical region 22, is an rRNA methyltransferase involved in ribosome maturation and RNA methylation. It has been reported to promote tumor progression in several malignancies. Although BUD23 has been implicated in drug resistance in lung cancer cells, its role in non‑small cell lung cancer (NSCLC) remains incompletely understood. In the present study, transcriptomic and proteomic datasets were analyzed to evaluate the expression of BUD23 in NSCLC and normal tissues, and Kaplan‑Meier survival analysis was performed to assess its prognostic significance. Immune infiltration algorithms were used to examine the correlation between BUD23 expression and tumor immune cell infiltration in NSCLC. Gene set enrichment analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and single‑cell enrichment analysis were conducted to explore the biological pathways associated with BUD23 expression. In vitro, the effect of BUD23 knockdown on the viability, motility and apoptosis of NSCLC cell lines was evaluated by Cell Counting Kit‑8, wound healing and Annexin V/PI flow cytometry assays, respectively, and the mRNA expression levels of potential downstream genes were quantified by reverse transcription‑quantitative PCR. BUD23 was found to be significantly upregulated in NSCLC and associated with poor patient survival. Immunogenomic analyses indicated that high BUD23 levels are correlated with reduced immune cell infiltration. GSEA, KEGG and single‑cell pathway enrichment analyses consistently implicated BUD23 in ‘DNA repair’ and ‘cell cycle’ pathways. In vitro, BUD23 knockdown suppressed the proliferation and migration of NSCLC cells, and reduced RNA polymerase II subunit J expression. Collectively, these findings suggest that BUD23 may contribute to the development and progression of NSCLC, and provide a strong basis for future mechanistic and clinical investigations.
View Figures

Figure 1

BUD23 expression is upregulated in
NSCLC based on TCGA, GTEx and CPTAC data. (A) Pan-cancer analysis
of BUD23 expression in tumor and normal tissues based on TCGA data.
Expression analysis of BUD23 in (B) LUAD and (C) LUSC between
cancer and normal tissues based on integrated TCGA and GTEx
datasets. Protein expression analysis of BUD23 in (D) lung
adenocarcinoma or (E) lung squamous cell carcinoma compared with
that in normal tissues based on CPTAC data. *P<0.05, **P<0.01
and ***P<0.001 as indicated. NSCLC, non-small cell lung cancer;
TCGA, The Cancer Genome Atlas; GTEx, Genotype-Tissue Expression;
CPTAC, Clinical Proteomic Tumor Analysis Consortium; LUAD, lung
adenocarcinoma; LUSC, lung squamous cell carcinoma; TPM,
transcripts per million; FC, fold change; T, tumor; N, normal.

Figure 2

BUD23 expression is upregulated in
NSCLC based on GEO dataset analyses. mRNA expression levels of
BUD23 in normal lung and primary NSCLC tissue based on GEO datasets
(A) GSE19188, (B) GSE30219 and (C) GSE40791. Expression levels of
BUD23 in lung cancer and matched adjacent normal tissues from GEO
datasets (D), GSE32665, (E) GSE40419, (F) GSE75037, (G) GSE7670,
(H) GSE27262, (I) GSE63459 and (J) GSE87340. ***P<0.001 as
indicated. NSCLC, non-small cell lung cancer; GEO, Gene Expression
Omnibus.

Figure 3

Elevated BUD23 levels are associated
with poor clinical outcomes in patients with NSCLC. Kaplan-Meier
survival curves comparing high and low BUD23 expression groups for
(A) OS (n=2,166), (B) FPS (n=1252) and (C) PPS (n=447), generated
using Kaplan-Meier Plotter. (D-F) Kaplan-Meier OS curves comparing
high and low BUD23 expression groups in NSCLC stratified by N
stage: (D) N0, (E) N1 and (F) N2. Association of BUD23 expression
with different clinical stages of NSCLC based on analysis of the
(G) GSE340419, (H) GSE31547 and (I) GSE31210 datasets. *P<0.05
and **P<0.01 as indicated. NSCLC, non-small cell lung cancer;
OS, overall survival; FPS, first progression survival; PPS,
post-progression survival; HR, hazard ratio (95% CI values).

Figure 4

Correlation between BUD23 and immune
characteristics in NSCLC analyzed using various algorithms based on
TCGA-LUAD and -LUSC data. Correlations of BUD23 expression with the
infiltration levels of (A) 6 immune cell types analyzed using
TIMER, (B) 8 immune cell types analyzed using EPIC, (C) 10 immune
cell types analyzed using MCPcounter and (D) 11 immune cell types
of analyzed using QUANTISEQ. Correlations of BUD23 expression with
(E) IPS score determined using the IPS algorithm and (F) stromal,
(G) immune and (H) ESTIMATE scores analyzed using ESTIMATE.
*P<0.05, **P<0.01 and ***P<0.001. NSCLC, non-small cell
lung cancer; TCGA, The Cancer Genome Atlas; LUAD, lung
adenocarcinoma; LUSC, lung squamous cell carcinoma; IPS,
immunophenoscore; DC, dendritic cell; CAFs, cancer-associated
fibroblasts; NK, natural killer; Tregs, regulatory T cells; MHC,
major histocompatibility complex; EC, effector cell; SC, suppressor
cell; CP, checkpoint molecule; AZ, antigen processing and
presentation machinery.

Figure 5

BUD23 is associated with DNA repair
and cell cycle pathways in NSCLC. Gene set enrichment analysis
analysis revealed that the Hallmark DNA repair gene set was
significantly enriched in patients with high BUD23 expression in
(A) TCGA-LUAD and (B) TCGA-LUSC cohorts. Kyoto Encyclopedia of
Genes and Genomes pathway analysis revealed that BUD23-correlated
genes (R2>0.3, P<0.05) were significantly enriched
in ‘cell cycle’ pathway in (C) TCGA-LUAD and (D) TCGA-LUSC.
Single-cell correlation analysis based on the E-MTAB-6149 dataset
in the CancerSEA database shows significant correlations between
BUD23 expression and the (E) ‘cell cycle’ and (F) ‘DNA repair’
functional states in NSCLC. NSCLC, non-small cell lung cancer;
TCGA, The Cancer Genome Atlas; LUAD, lung adenocarcinoma; LUSC,
lung squamous cell carcinoma; ES, enrichment score; FDR, false
discovery rate; -log10(P), -log10(P-value).

Figure 6

BUD23 knockdown suppresses the
proliferative and migration of NSCLC cells. (A) RT-qPCR was used to
quantify BUD23 mRNA levels in HBE cells and a panel of NSCLC cell
lines. Validation of BUD23 knockdown efficiency in (B) A549 and (C)
H1299 cells by RT-qPCR. Assessment of cell viability in (D) A549
and (E) H1299 cells via CCK-8 assay and cell migration in (F) A549
and (G) H1299 cells by wound healing assay (magnification, ×10).
CCK-8 assays of (H) A549 and (I) H1299 cells 24 h after BUD23
knockdown with or without subsequent co-culture with Jurkat T cells
for 48 h in Transwell chambers. (J) Quantification of apoptosis in
A549 and H1299 cells via Annexin V/PI flow cytometry. **P<0.01
and ***P<0.001 vs. HBE, NC, Con or as indicated. NSCLC,
non-small cell lung cancer; RT-qPCR, reverse
transcription-quantitative PCR; HBE, human bronchial epithelial;
CCK-8, Cell Counting Kit-8; NC, negative control; Con, control;
Si1/2, small interfering RNA targeting BUD23.

Figure 7

BUD23 knockdown significantly
downregulates POLR2J expression in non-small cell lung cancer. (A)
Venn diagram showing the intersection between LUAD GSEA core
enrichment genes (key genes driving Hallmark DNA repair pathway
enrichment) and LUSC GSEA core enrichment genes within the Hallmark
DNA repair gene set, identifying 49 common genes. (B) Venn diagram
showing the intersection between BUD23-correlated genes
(correlation index >0.3) derived from the TCGA-LUAD cohort and
BUD23-correlated genes (correlation index >0.3) derived from the
TCGA-LUSC cohort via multi-gene correlation analysis, yielding 79
overlapping genes. (C) Venn diagram showing the secondary
intersection between the 49 overlapping GSEA core enrichment genes
(from panel A) and the 79 overlapping BUD23-correlated genes (from
panel B), identifying 4 shared common genes: TAF6, POLR2J, RFC2 and
VPS37D. (D) Validation of TAF6, POLR2J, RFC2 and VPS37D mRNA
expression following BUD23 knockdown in A549 cells via reverse
transcription-quantitative PCR. Cell-cycle analysis in (E) A549 and
(F) H1299 cells following BUD23 knockdown. ***P<0.001 vs. Con.
POLR2J, RNA polymerase II subunit J; LUAD, lung adenocarcinoma;
GSEA, gene set enrichment analysis; LUSC, lung squamous cell
carcinoma; TCGA, The Cancer Genome Atlas; TAF6, TATA-box binding
protein associated factor 6; RFC2, replication factor C subunit 2;
VPS37D, vacuolar protein sorting-associated protein 37D; Con,
control; Si1, small interfering RNA targeting BUD23.
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Copy and paste a formatted citation
Spandidos Publications style
Tan Y, Ma J, Zhou J and Lu J: BUD23 is associated with malignancy and correlates with immune infiltration in NSCLC. Oncol Lett 31: 252, 2026.
APA
Tan, Y., Ma, J., Zhou, J., & Lu, J. (2026). BUD23 is associated with malignancy and correlates with immune infiltration in NSCLC. Oncology Letters, 31, 252. https://doi.org/10.3892/ol.2026.15608
MLA
Tan, Y., Ma, J., Zhou, J., Lu, J."BUD23 is associated with malignancy and correlates with immune infiltration in NSCLC". Oncology Letters 31.6 (2026): 252.
Chicago
Tan, Y., Ma, J., Zhou, J., Lu, J."BUD23 is associated with malignancy and correlates with immune infiltration in NSCLC". Oncology Letters 31, no. 6 (2026): 252. https://doi.org/10.3892/ol.2026.15608
Copy and paste a formatted citation
x
Spandidos Publications style
Tan Y, Ma J, Zhou J and Lu J: BUD23 is associated with malignancy and correlates with immune infiltration in NSCLC. Oncol Lett 31: 252, 2026.
APA
Tan, Y., Ma, J., Zhou, J., & Lu, J. (2026). BUD23 is associated with malignancy and correlates with immune infiltration in NSCLC. Oncology Letters, 31, 252. https://doi.org/10.3892/ol.2026.15608
MLA
Tan, Y., Ma, J., Zhou, J., Lu, J."BUD23 is associated with malignancy and correlates with immune infiltration in NSCLC". Oncology Letters 31.6 (2026): 252.
Chicago
Tan, Y., Ma, J., Zhou, J., Lu, J."BUD23 is associated with malignancy and correlates with immune infiltration in NSCLC". Oncology Letters 31, no. 6 (2026): 252. https://doi.org/10.3892/ol.2026.15608
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