High expression of PI4K2A predicted poor prognosis of colon adenocarcinoma (COAD) and correlated with immunity

Xinkun Huang; Yang Cao; Peng Bao; Bingye Zhu; Zhouyang Cheng

doi:10.1002/cam4.4895

High expression of PI4K2A predicted poor prognosis of colon adenocarcinoma (COAD) and correlated with immunity

Cancer Med. 2023 Jan;12(1):837-851. doi: 10.1002/cam4.4895. Epub 2022 May 30.

Authors

Xinkun Huang^#¹, Yang Cao^#², Peng Bao^#³, Bingye Zhu⁴, Zhouyang Cheng¹

Affiliations

¹ Department of General Surgery, Affiliated Hospital of Nantong, Nantong, Jiangsu Province, China.
² Department of Operation, Affiliated Hospital of Nantong, Nantong, Jiangsu Province, China.
³ Department of Critical Care Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
⁴ Department of Urology, Affiliated Nantong Hospital of Shanghai University/The Sixth People's Hospital of Nantong, Nantong, Jiangsu Province, China.

^# Contributed equally.

Abstract

Background: PI4K2A has been found to have a tumor-promoting role in various solid tumors and be involved in various biological procedures. In this article, we aim to investigate the prognostic values of PI4K2A and provide new insights in colon adenocarcinoma (COAD).

Methods: The Cancer Genome Atlas (TCGA) database, Human Protein Atlas online database, and UALCAN database were used to analyze the expression of PI4K2A in COAD and the survival of patients. Univariate and multifactorial Cox regression analyses were used to assess the prognosis of PI4K2A on COAD. GSEA was used to explore PI4K2A-related signaling pathways. In addition, the effect of PI4K2A on immune checkpoint inhibitors (ICIs) treatment was investigated by constructing a TIDE model and predicting the association between PI4K2A and anticancer drug sensitivity through the CellMiner database.

Results: In the TCGA database, PI4K2A was highly expressed in COAD and the similar results were verified by qRT-PCR. Survival analysis, utilizing Kaplan-Meier curves, revealed that COAD patients with high PI4K2A expression had a worse prognosis. In addition, PI4K2A expression was discovered to have been associated with T-stage, N-stage, and pathological stage by logistic analysis. Next, we utilized univariate and multifactorial Cox regression analyses to identify PI4K2A as an independent predictor. Additionally, GSEA analysis indicates that PI4K2A is enriched in MAPK signaling pathway, Toll-like receptor signaling pathway, etc. In COAD, PI4K2A was remarkably associated with the tumor immune microenvironment. In addition, by constructing a TIDE model, we discovered that COAD patients in the PI4K2A low-expression cohort were better treated with ICI. Finally, analysis of the CellMiner database predicted that PI4K2A was adversely correlated with the sensitivity of various anticancer drugs.

Conclusions: Our study suggests that PI4K2A may be a potential predictor of poor prognosis in COAD and a potential biomarker for early diagnosis, prognosis, and treatment.

Keywords: PI4K2A; biomarker; colon adenocarcinoma; immunity; prognosis.

MeSH terms

Adenocarcinoma* / drug therapy
Adenocarcinoma* / genetics
Colonic Neoplasms* / drug therapy
Colonic Neoplasms* / genetics
Databases, Factual
Humans
Immune Checkpoint Inhibitors
MAP Kinase Signaling System
Prognosis
Tumor Microenvironment

Substances

Immune Checkpoint Inhibitors
phosphatidylinositol phosphate 4-kinase