Screening and experimental validation of prognostic genes associated with B cell exhaustion in lung adenocarcinoma based on ordinary transcriptome data.
- 1Department of Thoracic Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.
- 2State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
- 3Department of Thoracic Surgery, Baodi Clinical College of Tianjin Medical University, Tianjin, China.
Abstract
B-cell exhaustion (BEX) has emerged as a critical mechanism in tumor immune evasion. However, the prognostic significance of B-cell exhaustion-related genes (BEX-RGs) and their potential as therapeutic targets in lung adenocarcinoma (LUAD) remain unclear. This study aimed to identify a BEX-RGs-based prognostic signature and elucidate its implications for LUAD immunotherapy. Transcriptomic data and BEX-RGs were obtained from public databases. Prognostic genes were obtained through univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Afterwards, a predictive model was constructed and validated. Further analyses yielded independent prognostic factors, and a nomogram was created. Additionally, enrichment analyses and immune microenvironment analyses were conducted to elucidate the underlying mechanisms of LUAD. Drug sensitivity analysis was conducted to identify drugs with differential sensitivity between groups, providing a basis for personalized treatment strategies. Immunohistochemical (IHC) staining was used to assess the protein expression of BEX-RGs in 90 LUAD specimens and paired distant normal lung tissues, and overall survival (OS) analysis was performed to evaluate their prognostic associations. In this study, five prognostic genes were identified: heparin-binding epidermal growth factor-like growth factor (HBEGF) and CD79A, CD101, adrenergic receptor β2 (ADRB2), and dipeptidase 2 (DPEP2). The developed prognostic model and nomogram had robust risk evaluation capability. Enrichment analyses highlighted immune dysregulation and metabolic alterations. High-risk patients exhibited reduced immune/stromal scores and heightened sensitivity to 36 chemotherapeutic agents. Five BEX-related prognostic genes associated with LUAD prognosis were identified, and the constructed model showed potential value for prognostic stratification. Differences in immune microenvironment, gene mutations and drug sensitivity between risk groups provide evidence for tumor immunity research and targeted therapy development. IHC and OS results confirmed that the expression trends of the five genes were consistent with the results of the bioinformatics analysis.
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BibTeX
@article{yang2026screening,
title = {{Screening and experimental validation of prognostic genes associated with B cell exhaustion in lung adenocarcinoma based on ordinary transcriptome data.}},
author = {Bo Yang and Guang-Shun Wang and Liang Zhang and Pan Yang and Jia-Qi Bao and Lin-Xiao Li and Lei Li and Ben Gao and Wei Li and Xiao-He Li},
journal = {Translational cancer research},
year = {2026},
month = oct,
doi = {10.21037/tcr-2026-1882},
url = {https://europepmc.org/article/MED/42997880},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Screening and experimental validation of prognostic genes associated with B cell exhaustion in lung adenocarcinoma based on ordinary transcriptome data.
AU - Bo Yang
AU - Guang-Shun Wang
AU - Liang Zhang
AU - Pan Yang
AU - Jia-Qi Bao
AU - Lin-Xiao Li
AU - Lei Li
AU - Ben Gao
AU - Wei Li
AU - Xiao-He Li
PY - 2026
DA - 2026/10/26
JO - Translational cancer research
DO - 10.21037/tcr-2026-1882
UR - https://europepmc.org/article/MED/42997880
AB - B-cell exhaustion (BEX) has emerged as a critical mechanism in tumor immune evasion. However, the prognostic significance of B-cell exhaustion-related genes (BEX-RGs) and their potential as therapeutic targets in lung adenocarcinoma (LUAD) remain unclear. This study aimed to identify a BEX-RGs-based prognostic signature and elucidate its implications for LUAD immunotherapy. Transcriptomic data and BEX-RGs were obtained from public databases. Prognostic genes were obtained through univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Afterwards, a predictive model was constructed and validated. Further analyses yielded independent prognostic factors, and a nomogram was created. Additionally, enrichment analyses and immune microenvironment analyses were conducted to elucidate the underlying mechanisms of LUAD. Drug sensitivity analysis was conducted to identify drugs with differential sensitivity between groups, providing a basis for personalized treatment strategies. Immunohistochemical (IHC) staining was used to assess the protein expression of BEX-RGs in 90 LUAD specimens and paired distant normal lung tissues, and overall survival (OS) analysis was performed to evaluate their prognostic associations. In this study, five prognostic genes were identified: heparin-binding epidermal growth factor-like growth factor (HBEGF) and CD79A, CD101, adrenergic receptor β2 (ADRB2), and dipeptidase 2 (DPEP2). The developed prognostic model and nomogram had robust risk evaluation capability. Enrichment analyses highlighted immune dysregulation and metabolic alterations. High-risk patients exhibited reduced immune/stromal scores and heightened sensitivity to 36 chemotherapeutic agents. Five BEX-related prognostic genes associated with LUAD prognosis were identified, and the constructed model showed potential value for prognostic stratification. Differences in immune microenvironment, gene mutations and drug sensitivity between risk groups provide evidence for tumor immunity research and targeted therapy development. IHC and OS results confirmed that the expression trends of the five genes were consistent with the results of the bioinformatics analysis.
SN - 2218-676X
SN - 2219-6803
ER -