Identification and Validation of an Anoikis-Related Prognostic Signature for Oesophageal Carcinoma Based on Integrated TCGA and GTEx Data

Hailun Li*
Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
*Corresponding email: helenli200549@foxmail.com
https://doi.org/10.71052/jdph/KOMP9905

Oesophageal carcinoma (ESCA) is a highly lethal malignancy for which reliable prognostic biomarkers remain limited. Anoikis resistance is recognised as a pivotal mechanism driving tumor progression and metastatic dissemination. This study aimed to develop a novel anoikis-related gene signature to predict overall survival in patients with ESCA. Ribonucleic acid (RNA)-sequencing data from The Cancer Genome Atlas (TCGA) oesophageal cancer cohort and normal oesophageal tissue samples from the Genotype-Tissue Expression (GTEx) project were integrated. Differentially expressed genes (DEGs) between tumor and normal tissues were intersected with curated anoikis-related gene sets. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression were sequentially applied to construct a prognostic signature. Model performance was validated using Kaplan-Meier survival analysis, Time-dependent Receiver Operating Characteristic (tdROC) curves, and calibration plots. A total of 263 anoikis-related DEGs were identified. Following LASSO and multivariate Cox analyses, a 16-gene signature was established, comprising growth arrest and deoxyribonucleic acid (DNA) damage inducible beta (GADD45B), bombesin receptor subtype 3 (BRS3), paired box 4 (PAX4), folate receptor gamma (FOLR3), interleukin 17A (IL17A), proline rich and Gla domain 3 (PRRG3), nuclear factor I C (NFIC), von Willebrand factor D and EGF domains (VWDE), G protein-coupled receptor 26 (GPR26), hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 (HCN1), GRAM domain containing 1C (GRAMD1C), calpain-12 (CAPN12), sodium/potassium transporting ATPase interacting 3 (NKAIN3), haptoglobin-related protein (HPR), cTAGE family member 15 (CTAGE15), and Rho GTPase Activating Protein 11B (ARHGAP11B). The risk score derived from this signature significantly stratified patients into high-risk and low-risk groups (p<0.0001). TdROC analysis demonstrated robust predictive accuracy, with area under the curve (AUC) values of 0.924, 0.935, and 0.952 for 1-year, 3-year, and 5-year overall survival, respectively. Calibration curves indicated excellent agreement between nomogram-predicted and observed survival probabilities. The 16-gene anoikis-related signature represents a robust and independent prognostic tool for ESCA and may facilitate personalised therapeutic decision-making.

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Li, H. (2026) Identification and Validation of an Anoikis-Related Prognostic Signature for Oesophageal Carcinoma Based on Integrated TCGA and GTEx Data. Journal of Disease and Public Health, 2(1), 45-54. https://doi.org/10.71052/jdph/KOMP9905

Published

28/05/2026