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中心体蛋白 78 在肌层浸润性膀胱癌中过表达,并与肿瘤分子亚型和突变特征相关。

Centrosome Protein 78 Is Overexpressed in Muscle-Invasive Bladder Cancer and Is Associated with Tumor Molecular Subtypes and Mutation Signatures.

机构信息

Department of Pathology, Shanghai Clinical College, Anhui Medical University, Hefei, Anhui, China (mainland).

Department of Pathology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China (mainland).

出版信息

Med Sci Monit. 2020 Oct 29;26:e925197. doi: 10.12659/MSM.925197.

Abstract

BACKGROUND Centrosome aberrations have long been linked to tumorigenesis. Centrosome protein 78 (CEP78) is a centrosome component that is required to regulate the cell cycle, but its role in bladder cancer has not been elucidated. MATERIAL AND METHODS Real-time quantitative polymerase chain reaction and immunohistochemistry were used to examine the expression of CEP78 in bladder cancer tissues and adjacent non-cancer tissues. RESULTS Analysis of the RNA-Seq data from the TCGA (The Cancer Genome Atlas) MIBC cohort (n=408) revealed that CEP78 was overexpressed in tumor tissues, which was confirmed with fresh-frozen and formalin-fixed paraffin-embedded specimens collected from 28 and 33 MIBC patients, respectively, in the present study. The clinicopathological relevance of CEP78 was further investigated. High CEP78 expression was found to be correlated with non-papillary histological type, luminal, basal-squamous and neuronal molecular subtypes, TP53 mutation, RB1 mutation, wild-type FGFR3, PPARG fusion and amplification, high total number of single-nucleotide variants, and high neoantigen load, but it was not associated with tumor stages or overall survival. CONCLUSIONS The results of this study suggest that CEP78 plays in a role in promoting the development of MIBC and could be a novel diagnostic and therapeutic target.

摘要

背景

中心体异常与肿瘤发生有关已有很长时间。中心体蛋白 78(CEP78)是一种中心体成分,对于调节细胞周期至关重要,但它在膀胱癌中的作用尚未阐明。

材料与方法

使用实时定量聚合酶链反应和免疫组织化学方法检测膀胱癌组织和相邻非癌组织中 CEP78 的表达。

结果

TCGA(癌症基因组图谱)MIBC 队列(n=408)的 RNA-Seq 数据分析显示,CEP78 在肿瘤组织中过表达,这一结果在本研究中通过分别来自 28 名和 33 名 MIBC 患者的新鲜冷冻和福尔马林固定石蜡包埋标本得到了证实。进一步研究了 CEP78 的临床病理相关性。高 CEP78 表达与非乳头样组织学类型、腔型、基底-鳞状和神经元分子亚型、TP53 突变、RB1 突变、野生型 FGFR3、PPARG 融合和扩增、高总单核苷酸变异数以及高新生抗原负荷相关,但与肿瘤分期或总生存期无关。

结论

本研究结果表明,CEP78 在促进 MIBC 的发展中发挥作用,可能是一种新的诊断和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d648/7607667/4aa3b34c4f37/medscimonit-26-e925197-g001.jpg

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