by Xudan Zhou, Qinglin Yang, Yuxin Zhang, Xiaoli Chen, Jin Luo, Guohui Ma, Wei Shu
2026,13(1);
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Abstract
To identify core prognostic markers and key pathways of lung squamous cell carcinoma (LSCC), this study adopted the interpretable Dual PASNet deep learning model with a dynamic pathway mask mechanism to screen survival-related pathways/genes, and systematically validated their prognostic value through multi-cohort verification, feature selection, and functional analysis. The model identified 10 survival-related core pathways in LSCC (P<0.01), with p53 signaling, cell cycle, and PI3K-Akt signaling pathways having the highest weights. Sixteen core genes showed significant expression differences between high- and low-risk groups in both TCGA-LUSC (internal) and GSE19804 (external) cohorts (*P<0.001), and 10 prognostic signature genes were further screened by LASSO regression. The 10-gene prognostic model exhibited robust risk stratification (Log-rank P=0.000765), with time-dependent ROC AUC of 0.709–0.780 at 6–60 months. Functional enrichment indicated significant enrichment in tumor malignant phenotype-related pathways (cell cycle, DNA replication). Immune analysis showed a close association with LSCC immunosuppressive microenvironment (more prominent in high-risk group), which was validated by single-cell transcriptome analysis (GSE131907) showing specific expression of signature genes in myeloid cells and T lymphocytes. This 10-gene prognostic signature has reliable prognostic predictive value for LSCC, reveals key molecular regulatory pathways and immune microenvironment characteristics, and provides potential molecular markers and a theoretical basis for precise prognostic evaluation and targeted therapy of LSCC.
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