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

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

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1344317

DOI=10.3389/fphar.2024.1344317

ISSN=1663-9812

ABSTRACT=<p>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 (<italic>p</italic> = 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 <italic>PKP1</italic> had no significant correlation with other traits at the gene level. <italic>PKP1</italic> was identified as a potential prognostic marker for ESCC, with upregulated expression observed in ESCC patients. <italic>In vitro</italic> experiments showed that the knockdown of <italic>PKP1</italic> inhibited ESCC cell proliferation and migration. These findings suggest that the novel HPRscore and <italic>PKP1</italic> may serve as prognostic tools and therapeutic targets for ESCC patients.</p>