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PI4K2A 的高表达预示着结直肠腺癌(COAD)的预后不良,并且与免疫相关。

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

机构信息

Department of General Surgery, Affiliated Hospital of Nantong, Nantong, Jiangsu Province, China.

Department of Operation, Affiliated Hospital of Nantong, Nantong, Jiangsu Province, China.

出版信息

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

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.

摘要

背景

PI4K2A 在各种实体瘤中具有促进肿瘤的作用,并参与各种生物学过程。本文旨在研究 PI4K2A 在结肠腺癌(COAD)中的预后价值,并提供新的见解。

方法

使用癌症基因组图谱(TCGA)数据库、人类蛋白质图谱在线数据库和 UALCAN 数据库分析 COAD 中 PI4K2A 的表达和患者的生存情况。使用单因素和多因素 Cox 回归分析评估 PI4K2A 对 COAD 的预后影响。GSEA 用于探索 PI4K2A 相关的信号通路。此外,通过构建 TIDE 模型研究 PI4K2A 对免疫检查点抑制剂(ICIs)治疗的影响,并通过 CellMiner 数据库预测 PI4K2A 与抗癌药物敏感性之间的关联。

结果

在 TCGA 数据库中,PI4K2A 在 COAD 中高表达,qRT-PCR 验证了这一结果。生存分析显示,PI4K2A 高表达的 COAD 患者预后较差。此外,逻辑分析发现 PI4K2A 表达与 T 分期、N 分期和病理分期有关。接下来,我们利用单因素和多因素 Cox 回归分析确定 PI4K2A 是一个独立的预测因子。此外,GSEA 分析表明,PI4K2A 在 MAPK 信号通路、Toll 样受体信号通路等信号通路中富集。在 COAD 中,PI4K2A 与肿瘤免疫微环境显著相关。此外,通过构建 TIDE 模型,我们发现 COAD 患者在 PI4K2A 低表达队列中对 ICI 的治疗效果更好。最后,通过分析 CellMiner 数据库预测 PI4K2A 与各种抗癌药物的敏感性呈负相关。

结论

本研究表明,PI4K2A 可能是 COAD 预后不良的潜在预测因子,也是早期诊断、预后和治疗的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/9844633/6b4620262bec/CAM4-12-837-g009.jpg

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