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前胶原赖氨酸、2-氧戊二酸5-双加氧酶1、2和3是透明细胞肾细胞癌患者潜在的预后指标。

Procollagen-lysine, 2-oxoglutarate 5-dioxygenases 1, 2, and 3 are potential prognostic indicators in patients with clear cell renal cell carcinoma.

作者信息

Xu Wen-Hao, Xu Yue, Wang Jun, Tian Xi, Wu Junlong, Wan Fang-Ning, Wang Hong-Kai, Qu Yuan-Yuan, Zhang Hai-Liang, Ye Ding-Wei

机构信息

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.

出版信息

Aging (Albany NY). 2019 Aug 25;11(16):6503-6521. doi: 10.18632/aging.102206.

DOI:10.18632/aging.102206
PMID:31446433
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6738415/
Abstract

Intratumoral fibrosis is a frequent histologic finding in highly vascularized clear cell renal cell carcinoma (ccRCC). Here, we investigated the expression of a family of collagen-modifying enzymes, procollagen-lysine, 2-oxoglutarate 5-dioxygenases 1, 2, and 3 (PLOD1/2/3), in ccRCC tissues and assessed the prognostic value of wild-type and genetically mutated PLOD1/2/3 for ccRCC patients. Normal kidney and ccRCC mRNA and protein expression datasets were obtained from Oncomine, The Cancer Genome Atlas, and Human Protein Atlas databases. Associations between PLOD1/2/3 expression, clinicopathological variables, and patient survival were evaluated using Cox regression and Kaplan-Meier analyses. PLOD1/2/3 mRNA and protein expression levels were significantly elevated in ccRCC tissues compared with normal kidney. Increased PLOD1/2/3 mRNA expression was significantly associated with advanced tumor stage, high pathological grade, and shorter progression-free and overall survival (all <0.01). Genetic mutation of PLOD1/2/3 was present in ~3% of ccRCC patients and was associated with significantly poorer prognosis compared with expression of wild-type PLOD1/2/3 (<0.001). This study thus identifies tumor expression of wild-type or mutated PLOD1/2/3 mRNA as a potential predictive biomarker for ccRCC patients and sheds light on the underlying molecular pathogenesis of ccRCC.

摘要

肿瘤内纤维化是高血管化透明细胞肾细胞癌（ccRCC）常见的组织学表现。在此，我们研究了胶原蛋白修饰酶家族原胶原赖氨酸2-氧代戊二酸5-双加氧酶1、2和3（PLOD1/2/3）在ccRCC组织中的表达，并评估了野生型和基因变异型PLOD1/2/3对ccRCC患者的预后价值。从Oncomine、癌症基因组图谱和人类蛋白质图谱数据库中获取正常肾脏和ccRCC的mRNA和蛋白质表达数据集。使用Cox回归和Kaplan-Meier分析评估PLOD1/2/3表达、临床病理变量与患者生存之间的关联。与正常肾脏相比，ccRCC组织中PLOD1/2/3的mRNA和蛋白质表达水平显著升高。PLOD1/2/3 mRNA表达增加与肿瘤晚期、高病理分级以及无进展生存期和总生存期缩短显著相关（均<0.01）。约3%的ccRCC患者存在PLOD1/2/3基因突变，与野生型PLOD1/2/3表达相比，其预后明显较差（<0.001）。因此，本研究确定野生型或突变型PLOD1/2/3 mRNA的肿瘤表达是ccRCC患者潜在的预测生物标志物，并阐明了ccRCC潜在的分子发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8852/6738415/d20a734ca493/aging-11-102206-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8852/6738415/73f336ba300a/aging-11-102206-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8852/6738415/4928834db75a/aging-11-102206-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8852/6738415/1606b8464de8/aging-11-102206-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8852/6738415/d20a734ca493/aging-11-102206-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8852/6738415/73f336ba300a/aging-11-102206-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8852/6738415/3e5b53edba3f/aging-11-102206-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8852/6738415/b1155fd70024/aging-11-102206-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8852/6738415/f680f333f6ef/aging-11-102206-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8852/6738415/48b171d20d55/aging-11-102206-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8852/6738415/4928834db75a/aging-11-102206-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8852/6738415/1606b8464de8/aging-11-102206-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8852/6738415/d20a734ca493/aging-11-102206-g008.jpg

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