Immune cell infiltration and drug sensitivity in PIK3CA-mutated esophageal squamous cell carcinoma: A TCGA database analysis

Shuo He; Qing Liu; Shujuan Luo; Bangwu Cai; Jiao Chen; Tianyuan Peng; Wei Wang; Tao Liu; Xiaomei Lu; Shutao Zheng

doi:10.1016/j.humimm.2024.111167

Immune cell infiltration and drug sensitivity in PIK3CA-mutated esophageal squamous cell carcinoma: A TCGA database analysis

Hum Immunol. 2024 Oct 26;85(6):111167. doi: 10.1016/j.humimm.2024.111167. Online ahead of print.

Authors

Shuo He¹, Qing Liu², Shujuan Luo¹, Bangwu Cai¹, Jiao Chen², Tianyuan Peng², Wei Wang², Tao Liu³, Xiaomei Lu⁴, Shutao Zheng⁵

Affiliations

¹ State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China; Department of Pathology, Basic Medicine College, Xinjiang Medical University, Urumqi 830017, China.
² State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China.
³ Department of Clinical Laboratory, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, 830011, China.
⁴ State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China. Electronic address: [email protected].
⁵ State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China; Department of Pathology, Basic Medicine College, Xinjiang Medical University, Urumqi 830017, China. Electronic address: [email protected].

PMID: 39490157
DOI: 10.1016/j.humimm.2024.111167

Abstract

Recent studies have increasingly focused on PIK3CA mutations in esophageal squamous cell carcinoma (ESCC); however, the clinicopathological significance of these mutations within the tumor microenvironment remains underexplored. This study aimed to evaluate and compare the clinicopathological significance of mutated PIK3CA in ESCC using in silico analyses of the ESCC dataset from the TCGA database. We assessed prognosis, differential expression, correlation with immune cell infiltration and immune checkpoint expression, heterogeneity, and drug sensitivity in comparison with wild-type PIK3CA. Our findings revealed that PIK3CA mutation is associated with increased tumor mutation burden and significantly correlated with the infiltration of CD4 naive and effector memory CD4 T cells. Additionally, ESCC cells harboring PIK3CA mutations exhibited reduced sensitivity to p38/JNK MAPK inhibitors compared to those with wild-type PIK3CA. Collectively, our in silico analysis suggests that mutational PIK3CA plays a role in resistance to p38 and JNK MAPK inhibitors in ESCC.

Keywords: Drug sensitivity; Esophageal squamous cell carcinoma (ESCC); Immune checkpoint; PIK3CA mutation; Prognosis; TCGA database.