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人类前列腺癌家族的基因组和转录组分析

Genome and transcriptome profiling of family in human prostate cancer.

作者信息

Lan Ruoxin, Jin Ben, Liu Yao-Zhong, Zhang Kun, Niu Tianhua, You Zongbing

机构信息

Department of Structural & Cellular Biology, Tulane University New Orleans, LA, USA.

Department of Biostatistics and Data Science, Tulane University New Orleans, LA, USA.

出版信息

Am J Clin Exp Urol. 2020 Aug 15;8(4):116-128. eCollection 2020.

Abstract

F-box and WD repeat domain containing (FBXW) family of E3 ligases has 10 members that ubiquitinate substrate proteins for proteasome-mediated degradation. Publicly archived datasets from The Cancer Genome Atlas (TCGA), Prostate Cancer Transcriptome Atlas (PCTA), and cBioPortal were analyzed for mRNA expression and genetic alterations of 10 genes. We found that mRNA expression was significantly decreased in primary prostate cancers compared to normal prostate tissues, whereas mRNA expression of was significantly increased in primary prostate cancers compared to normal prostate tissues. mRNA expression was also significantly decreased in breast invasive carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, lung squamous cell carcinoma, and uterine corpus endometrial carcinoma. In contrast, mRNA expression was significantly increased in cholangiocarcinoma, colon adenocarcinoma, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, pheochromocytoma and paraganglioma, and thyroid carcinoma. Compared to normal tissues, mRNA expression was significantly increased in breast invasive carcinoma, cholangiocarcinoma, kidney chromophobe, kidney renal clear cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, prostate adenocarcinoma, thyroid carcinoma, and uterine corpus endometrial carcinoma, whereas mRNA expression was only significantly decreased in colon adenocarcinoma. There were not any significant differences in gene copy number gains, losses, or gene simple somatic mutations between primary prostate cancers and normal prostate tissues. The mRNA expression levels of , and were significantly higher in metastatic castration-resistant prostate cancers (mCRPCs) than primary prostate cancers, whereas mRNA expression levels of and were significantly lower in mCRPCs than primary prostate cancers. All 10 genes had significantly more overall gene alterations including gene amplifications in mCRPCs than primary prostate cancers. and 7 had significantly more gene deep deletions in mCRPCs than primary prostate cancers and had significantly more gene missense mutations in mCRPCs than primary prostate cancers. Our findings suggest that different genes have differential mRNA expression in prostate cancer and other cancer types and their gene amplifications are significantly more in mCRPCs than primary prostate cancers. mRNA expression is consistently decreased in primary prostate cancers compared to normal prostate tissues.

摘要

包含F-box和WD重复结构域的E3泛素连接酶(FBXW)家族有10个成员,可使底物蛋白泛素化,进而通过蛋白酶体介导进行降解。我们分析了来自癌症基因组图谱(TCGA)、前列腺癌转录组图谱(PCTA)和cBioPortal的公开存档数据集,以研究10个基因的mRNA表达和基因改变情况。我们发现,与正常前列腺组织相比,原发性前列腺癌中mRNA表达显著降低,而与正常前列腺组织相比,原发性前列腺癌中mRNA表达显著升高。在乳腺浸润性癌、多形性胶质母细胞瘤、头颈部鳞状细胞癌、肺鳞状细胞癌和子宫内膜癌中,mRNA表达也显著降低。相比之下,在胆管癌、结肠腺癌、肾透明细胞癌、肾乳头状细胞癌、肝细胞癌、肺腺癌、嗜铬细胞瘤和副神经节瘤以及甲状腺癌中,mRNA表达显著升高。与正常组织相比,在乳腺浸润性癌、胆管癌、肾嫌色细胞癌、肾透明细胞癌、肝细胞癌、肺腺癌、肺鳞状细胞癌、前列腺腺癌、甲状腺癌和子宫内膜癌中,mRNA表达显著升高,而mRNA表达仅在结肠腺癌中显著降低。原发性前列腺癌和正常前列腺组织之间在基因拷贝数增加、缺失或基因单发性体细胞突变方面没有任何显著差异。与原发性前列腺癌相比,转移性去势抵抗性前列腺癌(mCRPC)中、和的mRNA表达水平显著更高,而mCRPC中、的mRNA表达水平显著低于原发性前列腺癌。与原发性前列腺癌相比,所有10个基因在mCRPC中的总体基因改变(包括基因扩增)显著更多。与原发性前列腺癌相比,mCRPC中和7有显著更多的基因深度缺失,且mCRPC中有显著更多的基因错义突变。我们的研究结果表明,不同的基因在前列腺癌和其他癌症类型中具有不同的mRNA表达,并且它们在mCRPC中的基因扩增显著多于原发性前列腺癌。与正常前列腺组织相比,原发性前列腺癌中mRNA表达持续降低。

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