Work

Construction and cross-cohort evaluation of a shared metabolic reprogramming–related gene signature in esophageal and lung squamous cell carcinoma

Year: 2026

Type: article

Abstract: We investigated directionally consistent metabolic alterations in esophageal squamous cell carcinoma (ESCC) and lung squamous cell carcinoma (LUSC) and developed a pooled prognostic risk score. TCGA and GTEx data were used to identify shared differentially expressed metabolic genes. Candidates were screened by cancer-type-stratified Cox regression and LASSO; the eight largest absolute coefficients among 10 genes retained at lambda.min formed the final score. Apparent TCGA performance was evaluated with a 1,000-resample full-pipeline bootstrap. Cancer-balanced, cross-cancer, and GEO analyses assessed robustness and transportability. Fourteen candidates derived from 137 strict shared metabolic aberrant genes yielded an eight-gene score. Higher scores were associated with poorer overall survival in TCGA-LUSC (HR 2.71, 95% CI 1.87–3.93) and the merged cohort (HR 2.72, 95% CI 1.92–3.85), but the association was borderline in TCGA-ESCC (P = 0.058). The optimism-corrected C-index was 0.652 and the corrected 3-year calibration slope was 0.841. Cancer-balanced and bidirectional analyses preserved the adverse direction but showed reduced stability. In GSE53622, cohort-standardized analysis supported transportability (HR 1.82, P = 0.032), whereas strict fixed-parameter transfer was attenuated (HR 1.39, P = 0.218). The complete model was not evaluable in GSE73403 because ADH1B was unavailable; the exploratory reduced seven-gene score showed a borderline association (P = 0.051). The pooled score showed moderate optimism-corrected performance and limited cross-cohort transportability. It did not establish equivalent effects across ESCC and LUSC or a platform-independent clinical model. Prospective and functional validation are required.

Source: Discover Oncology

DOI: 10.1007/s12672-026-06006-9

Authors: Jian Liu, Xinlei Xiao, Xiangyan Liu, Bin Jiang, Shihao Bao, Zhongwei Xin

Institutions: Shandong Provincial Hospital, Shandong First Medical University, Jinan Central Hospital

Language: English

Topic: Cancer, Hypoxia, and Metabolism

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,690