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瞬时受体电位通道蛋白M4(TRPM4)和瞬时受体电位阳离子通道亚家族V成员2(TRPV2)是葡萄膜黑色素瘤(UVM)中两种新型的预后生物标志物和有前景的靶向治疗靶点。

TRPM4 and TRPV2 are two novel prognostic biomarkers and promising targeted therapy in UVM.

作者信息

Wang Jiong, Qiao Sen, Liang Shenzhi, Qian Cheng, Dong Yi, Pei Minghang, Wang Hongmei, Wan Guangming

机构信息

Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an, China.

出版信息

Front Mol Biosci. 2022 Aug 23;9:985434. doi: 10.3389/fmolb.2022.985434. eCollection 2022.

Abstract

Uveal melanoma (UVM) is the most common primary intraocular malignancy tumor in adults. Almost 50% of UVM patients develop metastatic disease, and is usually fatal within 1 year. However, the mechanism of etiology remains unclear. The lack of prognostic, diagnostic and therapeutic biomarkers is a main limitation for clinical diagnosis and treatment. The transient receptor potential (TRP) channels play important roles in the occurrence and development of tumors, which may have the potential as a therapeutic target for UVM. This current study aimed to identify the potential effect and function of the TRPs that could provide survival prediction and new insight into therapy for UVM. Based on the transcriptome data and potential key genes of UVM were screened using the Cancer Genome Atlas (TCGA) databases, Gene expression analysis showed the expression of TRPM4, TRPV2 and other TRPs was high levels in UVM. Using survival analysis, we screened out that the high expression of TRPM4 and TRPV2 was negatively correlated with the prognosis of UVM patients. Cox regression analysis and functional enrichment analysis further indicated that TRPM4 and TRPV2 were the most convincing therapeutic targets of UVM, and the majority of genes involved in ferroptosis pathways in UVM showed positively correlated with the expression levels of TRPM4 and TRPV2. In conclusion, TRPM4 and TRPV2 were considered as two novel prognostic biomarkers and a promising targeted therapy in UVM.

摘要

葡萄膜黑色素瘤(UVM)是成人中最常见的原发性眼内恶性肿瘤。几乎50%的UVM患者会发生转移性疾病,且通常在1年内死亡。然而,其病因机制仍不清楚。缺乏预后、诊断和治疗生物标志物是临床诊断和治疗的主要限制因素。瞬时受体电位(TRP)通道在肿瘤的发生和发展中起重要作用,可能具有作为UVM治疗靶点的潜力。本研究旨在确定TRP的潜在作用和功能,为UVM的生存预测和治疗提供新的见解。基于转录组数据,利用癌症基因组图谱(TCGA)数据库筛选出UVM的潜在关键基因,基因表达分析显示TRPM4、TRPV2和其他TRP在UVM中表达水平较高。通过生存分析,我们筛选出TRPM4和TRPV2的高表达与UVM患者的预后呈负相关。Cox回归分析和功能富集分析进一步表明,TRPM4和TRPV2是UVM最有说服力的治疗靶点,UVM中大多数参与铁死亡途径的基因与TRPM4和TRPV2的表达水平呈正相关。总之,TRPM4和TRPV2被认为是UVM的两种新型预后生物标志物和一种有前景的靶向治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b8e/9445434/921ac7481267/fmolb-09-985434-g001.jpg

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