Zheng Danxi, Long Siyu, Xi Mingrong
Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, No. 20, Third Section of People's South Road, Chengdu 610041, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Chengdu 610041, China.
Int J Mol Sci. 2023 Jul 25;24(15):11912. doi: 10.3390/ijms241511912.
The exact role of Transient receptor potential melastatin 2 (TRPM2) in tumor progression and immunomodulation remains elusive. We comprehensively investigated the expression pattern, diagnostic value, prognostic impact, genetic and epigenetic alterations of TRPM2 in pan-cancer. Then, we explored underlying pathways associated with TRPM2 and immune-related signatures. Ovarian cancer (OV) specimens were enrolled to test the expression of TRPM2 by immunohistochemistry and RT-qPCR. OV cell A2780 transfected with shRNA targeting TRPM2 was used in subsequent experiments. TRPM2 was aberrantly expressed and associated with unfavorable prognosis across various cancers. It possesses significant diagnostic values with AUC > 0.90. TRPM2 participated in pathways mediating immunoregulation and tumorigenesis. The expression of TRPM2 was significantly correlated with tumor microenvironment scores, tumor-stemness index, macrophages infiltration, immune checkpoints, and immune-related genes. OV single-cell datasets also indicated that TRPM2 was predominantly distributed on macrophages and malignancies. The overexpressed TRPM2 in OV tissues was validated at both the mRNA and protein levels. TRPM2 expression was significantly correlated with type2 macrophage marker CD206. Knockdown of TRPM2 inhibited OV cell proliferation and promoted apoptosis. Overall, TRPM2 has relevance to an immunosuppressive tumor microenvironment by modulating macrophage. It could serve as a powerful biomarker for tumor screening and prognosis, and a potential therapeutic target for tumor treatment, especially for OV.
瞬时受体电位褪黑素2（TRPM2）在肿瘤进展和免疫调节中的具体作用仍不清楚。我们全面研究了TRPM2在泛癌中的表达模式、诊断价值、预后影响、基因和表观遗传改变。然后，我们探索了与TRPM2相关的潜在通路和免疫相关特征。纳入卵巢癌（OV）标本，通过免疫组织化学和RT-qPCR检测TRPM2的表达。随后的实验使用了用靶向TRPM2的shRNA转染的OV细胞A2780。TRPM2在各种癌症中异常表达，并与不良预后相关。它具有显著的诊断价值，AUC>0.90。TRPM2参与介导免疫调节和肿瘤发生的通路。TRPM2的表达与肿瘤微环境评分、肿瘤干性指数、巨噬细胞浸润、免疫检查点和免疫相关基因显著相关。OV单细胞数据集也表明TRPM2主要分布在巨噬细胞和恶性肿瘤上。OV组织中TRPM2的过表达在mRNA和蛋白质水平均得到验证。TRPM2表达与2型巨噬细胞标志物CD206显著相关。敲低TRPM2可抑制OV细胞增殖并促进凋亡。总体而言，TRPM2通过调节巨噬细胞与免疫抑制性肿瘤微环境相关。它可作为肿瘤筛查和预后的有力生物标志物，以及肿瘤治疗的潜在靶点，尤其是对于OV。
