Development and verification of a hypoxia- and immune-associated prognosis signature for esophageal squamous cell carcinoma

Lian Lian; Shi-Bing Teng; You-You Xia; Xiao-Ming Shen; Yan Zheng; Shu-Guang Han; Wen-Jie Wang; Xue-Fei Xu; Chong Zhou

doi:10.21037/jgo-22-69

Development and verification of a hypoxia- and immune-associated prognosis signature for esophageal squamous cell carcinoma

J Gastrointest Oncol. 2022 Apr;13(2):462-477. doi: 10.21037/jgo-22-69.

Authors

Lian Lian^#¹, Shi-Bing Teng^#², You-You Xia^#³, Xiao-Ming Shen¹, Yan Zheng¹, Shu-Guang Han⁴, Wen-Jie Wang⁵, Xue-Fei Xu⁴, Chong Zhou⁶

Affiliations

¹ Department of Oncology, Suzhou Xiangcheng People's Hospital, Suzhou, China.
² Department of Thoracic Surgery, Suzhou Xiangcheng People's Hospital, Suzhou, China.
³ Department of Radiation Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University (The First People's Hospital of Lianyungang), Lianyungang, China.
⁴ Department of General Surgery, Suzhou Xiangcheng People's Hospital, Suzhou, China.
⁵ Department of Radio-Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
⁶ Department of Radiation Oncology, Xuzhou Central Hospital, Xuzhou, China.

^# Contributed equally.

Abstract

Background: Esophageal cancer is one of the most common gastrointestinal malignancies worldwide, with high morbidity and mortality in China. The clinical importance of the interaction between hypoxia and immune status in the tumor microenvironment has been established in esophageal squamous cell carcinoma (ESCC). This study aims to develop a new hypoxia- and immune-based gene signature to predict the survival of ESCC patients.

Methods: The RNA-sequencing and clinical data of 173 cases of ESCC and 271 normal tissues were obtained from The Cancer Genome Atlas (TCGA) data portal and the Genotype-Tissue Expression (GTEx) database. Hypoxia-related genes (HRGs) and immune-related genes (IRGs) were retrieved from publicly shared data. Differentially expressed gene (DEG) analyses were carried out by the DESeq2 method using the edgeR package in R. Based on the intersection of the DEGs and HRGs/IRGs, differentially expressed HRGs (DEHRGs) and differentially expressed IRGs (DEIRGs) were obtained. DEHRGs and DEIRGs associated with prognosis were evaluated using univariate Cox proportional hazards analysis. A prognostic risk score model was constructed according to the genes acquired through Cox regression. Univariate analysis and Cox proportional hazards analysis were used to determine the independent prognostic factors related to prognosis. A nomogram was developed to predict the 1-, 2-, and 3-year overall survival (OS) probability.

Results: A total of 73 intersecting genes were obtained as DEHRGs and a total of 548 intersecting genes were obtained as DEIRGs. The risk score was established using 8 genes (FABP7, TLR1, SYTL1, APLN, OSM, EGFR, IL17RD, MYH9) acquired from univariate Cox analysis. Based on this 8-gene-based risk score, a risk prognosis classifier was constructed to classify the samples into high- and low-risk groups according to the median risk score. The nomogram model was constructed to predict the OS of ESCC patients.

Conclusions: The hypoxia- and immune-based gene signature might serve as a prognostic classifier for clinical decision-making regarding individualized management, follow-up plans, and treatment strategies for ESCC patients.

Keywords: Esophageal cancer; hypoxia; immune; microenvironment; prognosis.