# Multi-cohort validation based on a novel prognostic signature of anoikis for predicting prognosis and immunotherapy response of esophageal squamous cell carcinoma

## TL;DR

This study identifies a new gene signature based on anoikis-related genes that can predict survival and immunotherapy response in esophageal squamous cell carcinoma patients.

## Contribution

A novel prognostic signature of anoikis-related genes is developed and validated for predicting ESCC prognosis and immunotherapy response.

## Key findings

- Two subgroups of ESCC patients with distinct survival outcomes were identified using anoikis-related genes.
- A four-gene signature reliably predicts immunotherapy response across multiple cohorts.
- Risk groups differ in tumor infiltration, immune function, and mutation burden.

## Abstract

Immunotherapy is recognized as an effective and promising treatment modality that offers a new approach to cancer treatment. However, identifying responsive patients remains challenging. Anoikis, a distinct form of programmed cell death, plays a crucial role in cancer progression and metastasis. Thus, we aimed to investigate prognostic biomarkers based on anoikis and their role in guiding immunotherapy decisions for esophageal squamous cell carcinoma (ESCC). By consensus clustering, the GSE53624 cohort of ESCC patients was divided into two subgroups based on prognostic anoikis-related genes (ARGs), with significant differences in survival outcomes between the two subgroups. Subsequently, we constructed an ARGs signature with four genes, and its reliability and accuracy were validated both internally and externally. Additional, different risk groups showed notable variances in terms of immunotherapy response, tumor infiltration, functional enrichment, immune function, and tumor mutation burden. Notably, the effectiveness of the signature in predicting immunotherapy response was confirmed across multiple cohorts, including GSE53624, GSE53625, TCGA-ESCC, and IMvigor210, highlighting its potential utility in predicting immunotherapy response. In conclusion, the ARGs signature has the potential to serve as an innovative and dependable prognostic biomarker for ESCC, facilitating personalized treatment strategies in this field, and may represent a valuable new tool for guiding ESCC immunotherapy decision-making.