Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.
Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, Guangxi, China.
Apoptosis. 2024 Feb;29(1-2):243-266. doi: 10.1007/s10495-023-01884-8. Epub 2023 Sep 5.
A particular GTPase-activating protein called RACGAP1 is involved in apoptosis, proliferation, invasion, metastasis, and drug resistance in a variety of malignancies. Nevertheless, the role of RACGAP1 in pan-cancer was less studied, and its value of the expression and prognostic of nasopharyngeal carcinoma (NPC) has not been explored. Hence, the goal of this study was to investigate the oncogenic and immunological roles of RACGAP1 in various cancers and its potential value in NPC. We comprehensively analyzed RACGAP1 expression, prognostic value, function, methylation levels, relationship with immune cells, immune infiltration, and immunotherapy response in pan-cancer utilizing multiple databases. The results discovered that RACGAP1 expression was elevated in most cancers and suggested poor prognosis, which could be related to the involvement of RACGAP1 in various cancer-related pathways such as the cell cycle and correlated with RACGAP1 methylation levels, immune cell infiltration and reaction to immunotherapy, and chemoresistance. RACGAP1 could inhibit anti-tumor immunity and immunotherapy responses by fostering immune cell infiltration and cytotoxic T lymphocyte dysfunction. Significantly, we validated that RACGAP1 mRNA and protein were highly expressed in NPC. The Gene Expression Omnibus database revealed that elevated RACGAP1 expression was associated with shorter PFS in patients with NPC, and RACGAP1 potentially influenced cell cycle progression, DNA replication, metabolism, and immune-related pathways, resulting in the recurrence and metastasis of NPC. This study indicated that RACGAP1 could be a potential biomarker in pan-cancer and NPC.
一种名为 RACGAP1 的特殊 GTPase 激活蛋白参与多种恶性肿瘤的凋亡、增殖、侵袭、转移和耐药。然而,RACGAP1 在泛癌中的作用研究较少,其在鼻咽癌(NPC)中的表达和预后价值尚未得到探索。因此,本研究旨在探讨 RACGAP1 在各种癌症中的致癌和免疫作用及其在 NPC 中的潜在价值。我们综合利用多个数据库分析了 RACGAP1 在泛癌中的表达、预后价值、功能、甲基化水平、与免疫细胞的关系、免疫浸润和免疫治疗反应。结果发现,RACGAP1 在大多数癌症中表达上调,并提示预后不良,这可能与 RACGAP1 参与细胞周期等多种癌症相关途径有关,并与 RACGAP1 甲基化水平、免疫细胞浸润和对免疫治疗的反应以及化疗耐药性相关。RACGAP1 可以通过促进免疫细胞浸润和细胞毒性 T 淋巴细胞功能障碍来抑制抗肿瘤免疫和免疫治疗反应。值得注意的是,我们验证了 RACGAP1 在 NPC 中mRNA 和蛋白表达均较高。基因表达综合数据库显示,RACGAP1 表达升高与 NPC 患者的 PFS 较短相关,RACGAP1 可能影响细胞周期进程、DNA 复制、代谢和免疫相关途径,导致 NPC 的复发和转移。本研究表明,RACGAP1 可能是泛癌和 NPC 的潜在生物标志物。