Wang Yang, Xie Youbang, Qian Luomeng, Ding Ran, Pang Rongqing, Chen Ping, Zhang Qing, Zhang Sihe
Department of Cell Biology, School of Medicine, Nankai University, Tianjin, China.
Department of Hematology and Rheumatology, Qinghai Provincial People's Hospital, Xining, Qinghai, China.
Front Pharmacol. 2024 Jul 19;15:1445170. doi: 10.3389/fphar.2024.1445170. eCollection 2024.
RAB42 (Ras-related protein 42) is a new small GTPase that controls the vesicular trafficking from endosomes to trans-Golgi network in mammalian cells. However, the role of RAB42 in multiple cancers, especially in liver hepatocellular carcinoma (LIHC), has not been well investigated.
A variety of cancer-related databases and online tools, including TCGA, GTEx, TARGET, QUANTISEQ, EPIC, RNAactDrug, CTR-DB, TIMER algorithms and Sangerbox, were applied to explore the correlation of RAB42 expression with prognosis, immune microenvironment, immune regulatory network, RNA modification, pathway activation and drug sensitivity in pan-cancer. The prognostic, immunomodulatory and tumor-promoting effects of RAB42 were verified in various malignancies and determined by a series of cellular experiments.
RAB42 is significantly overexpressed in most cancers with advanced pathological stages. Its overexpression is correlated with poor survival in pan-cancer. RAB42 overexpression has a high diagnostic accuracy of various cancers (AUC > 0.80). RAB42 overexpression not only correlates with distinct stromal immune infiltration and level of immune checkpoint molecules, but also associates with weak immune cell infiltration, immunomodulatory genes expression, and immunotherapeutic response to immune checkpoint inhibitors (ICIs). Additionally, RAB42 overexpression correlates with enhanced expression of m6A RNA methylation-related genes (MRGs) and its interactors. Moreover, overexpression of RAB42 serves as a drug-resistant marker to certain chemotherapies and acts as a potential biomarker for LIHC. Notably, RAB42 overexpression or activation promotes the cellular proliferation, migration and invasion of LIHC.
Overexpressed RAB42 serves as a potential prognostic biomarker and therapeutic target in pan-cancer, especially in LIHC.
RAB42（Ras相关蛋白42）是一种新的小GTP酶，可控制哺乳动物细胞中从内体到反式高尔基体网络的囊泡运输。然而，RAB42在多种癌症，特别是在肝细胞癌（LIHC）中的作用尚未得到充分研究。
应用多种癌症相关数据库和在线工具，包括TCGA、GTEx、TARGET、QUANTISEQ、EPIC、RNAactDrug、CTR-DB、TIMER算法和Sangerbox，探讨RAB42表达与泛癌预后、免疫微环境、免疫调节网络、RNA修饰、通路激活和药物敏感性的相关性。RAB42的预后、免疫调节和促肿瘤作用在各种恶性肿瘤中得到验证，并通过一系列细胞实验确定。
RAB42在大多数病理分期较晚的癌症中显著过表达。其过表达与泛癌患者的不良生存相关。RAB42过表达对各种癌症具有较高的诊断准确性（AUC>0.80）。RAB42过表达不仅与不同的基质免疫浸润和免疫检查点分子水平相关，还与免疫细胞浸润较弱、免疫调节基因表达以及对免疫检查点抑制剂（ICIs）的免疫治疗反应相关。此外，RAB42过表达与m6A RNA甲基化相关基因（MRGs）及其相互作用因子的表达增强相关。此外，RAB42过表达作为某些化疗的耐药标志物，是LIHC的潜在生物标志物。值得注意的是，RAB42过表达或激活促进了LIHC的细胞增殖、迁移和侵袭。
过表达的RAB42作为泛癌，尤其是LIHC中的潜在预后生物标志物和治疗靶点。
