综合分析确定了 ARHGAP 家族的三个成员在胰腺腺癌中的作用。

Integrated analysis identified the role of three family members of ARHGAP in pancreatic adenocarcinoma.

机构信息

Department of Hepatobiliary Surgery, The First People's Hospital of Lianyungang, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, 222000, Jiangsu, China.

Jinzhou Medical University, Jinzhou, 121001, Liaoning, China.

出版信息

Sci Rep. 2024 May 23;14(1):11790. doi: 10.1038/s41598-024-62577-z.

DOI:10.1038/s41598-024-62577-z

PMID:38783033

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11116390/

Abstract

The Rho GTPase activating protein family (ARHGAPs) is expressed in pancreatic adenocarcinoma (PAAD) but its function is unclear. The aim of this study was to explore the role and potential clinical value of ARHGAPs in PAAD. Using TCGA and GEO databases to analyze expression of ARHGAPs in PAAD and normal tissues. Survival curve was drawn by Kaplan-Meier. ARHGAPs were integrated analyzed by GEPIA2, TIMER, UCLCAN, cBioPortal and R language. Protein level and prognostic value were evaluated via IHC staining or survival analysis. We totally identify 18 differentially expressed (DE) ARHGAPs in PAAD. Among the 18 DE genes, 8 were positively correlated with tumor grade; abnorrmal expression of 5 was positively correlated with copy number variation; expression of 4 was positively correlated with promoter hypomethylation. Multivariate Cox regression identified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors of PAAD. The function of ARHGAPs was mainly related to GTPase activity and signaling, axon guidance, proteoglycans in cancer and focal adhesion. Expression of 7 ARHGAPs was strongly correlated with immune infiltration. Immunohistochemistry showed increased protein levels of ARHGAP5, ARHGAP11A, and ARHGAP12 in PAAD tissues. Survival analysis confirmed a negative correlation between ARHGAP5, ARHGAP11A, and ARHGAP12 expression and patient prognosis. Multivariate Cox regression proved ARHGAP5, ARHGAP11A, and ARHGAP12 could serve as independent prognostic indicators for PAAD. Finally, this study verified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors in PAAD, suggesting their significance for the diagnosis and treatment of PAAD.

摘要

Rho GTPase 激活蛋白家族 (ARHGAPs) 在胰腺导管腺癌 (PAAD) 中表达，但功能尚不清楚。本研究旨在探讨 ARHGAPs 在 PAAD 中的作用及其潜在的临床价值。使用 TCGA 和 GEO 数据库分析 ARHGAPs 在 PAAD 和正常组织中的表达。通过 Kaplan-Meier 绘制生存曲线。通过 GEPIA2、TIMER、UCLCAN、cBioPortal 和 R 语言对 ARHGAPs 进行综合分析。通过 IHC 染色或生存分析评估蛋白水平和预后价值。我们总共鉴定了 18 个在 PAAD 中差异表达 (DE) 的 ARHGAPs。在这 18 个差异基因中，有 8 个与肿瘤分级呈正相关；5 个异常表达与拷贝数变异呈正相关；4 个表达与启动子低甲基化呈正相关。多因素 Cox 回归分析确定 ARHGAP5、ARHGAP11A 和 ARHGAP12 为 PAAD 的独立预后因素。ARHGAPs 的功能主要与 GTPase 活性和信号转导、轴突导向、癌症中的蛋白聚糖和焦点黏附有关。7 个 ARHGAPs 的表达与免疫浸润呈强相关性。免疫组织化学显示 ARHGAP5、ARHGAP11A 和 ARHGAP12 在 PAAD 组织中的蛋白水平升高。生存分析证实 ARHGAP5、ARHGAP11A 和 ARHGAP12 的表达与患者预后呈负相关。多因素 Cox 回归证明 ARHGAP5、ARHGAP11A 和 ARHGAP12 可作为 PAAD 的独立预后指标。最后，本研究验证了 ARHGAP5、ARHGAP11A 和 ARHGAP12 是 PAAD 的独立预后因素，提示它们对 PAAD 的诊断和治疗具有重要意义。