Identification and validation of prognostic and immunotherapeutic responses in esophageal squamous carcinoma based on hypoxia phenotype-related genes

Kai Xie; Zhe Chen; Jian Feng; Liangbin Pan; Nan Wang; Jing Luo; Yu Yao; Haitao Ma; Yu Feng; Wei Jiang

doi:10.3389/fphar.2024.1344317

Identification and validation of prognostic and immunotherapeutic responses in esophageal squamous carcinoma based on hypoxia phenotype-related genes

Front Pharmacol. 2024 Mar 7:15:1344317. doi: 10.3389/fphar.2024.1344317. eCollection 2024.

Authors

Kai Xie^#¹, Zhe Chen^#¹, Jian Feng^#², Liangbin Pan³, Nan Wang¹, Jing Luo⁴, Yu Yao⁵, Haitao Ma^{1

3}, Yu Feng³, Wei Jiang¹

Affiliations

¹ Department of Thoracic Surgery, The Fourth Affiliated Hospital of Soochow University, Suzhou, China.
² Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
⁴ Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
⁵ Department of Respiratory Medicine, Nanjing Second Hospital, Nanjing, China.

^# Contributed equally.

Abstract

The study aimed to investigate the clinical significance of the interaction between hypoxia and the immune system in esophageal squamous cell carcinoma (ESCC) microenvironment. A comprehensive evaluation of 13 hypoxia phenotype-related genes (HPRs) was conducted using data from TCGA-ESCC and two GEO cohorts. Three distinct HPRclusters were identified, and the HPRscore was established as an independent prognostic factor (p = 0.001), with higher scores indicating poorer prognosis. The HPRscore was validated in various immunotherapy cohorts, demonstrating its efficacy in evaluating immunotherapy and chemotherapy outcomes. Additionally, phenome-wide association study (PheWAS) analysis showed that PKP1 had no significant correlation with other traits at the gene level. PKP1 was identified as a potential prognostic marker for ESCC, with upregulated expression observed in ESCC patients. In vitro experiments showed that the knockdown of PKP1 inhibited ESCC cell proliferation and migration. These findings suggest that the novel HPRscore and PKP1 may serve as prognostic tools and therapeutic targets for ESCC patients.

Keywords: PKP1; PheWAS; Prognosis; esophageal squamous cell carcinoma; hypoxia; immunotherapy; tumor microenvironment.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the National Natural Science Foundation of China (Nos. 82273325, 82203561), Medical and industrial collaborative innovation research project (No. SZM2021005), Suzhou Ke Jiao Xing Wei Youth Science and Technology Projects (Nos. KJXW2022006, KJXW2022084), Postgraduate Research and Practice Innovation Program of Jiangsu Province (No. KYCX23_3275).