Comprehensive Analysis of HMCN1 Somatic Mutation in Clear Cell Renal Cell Carcinoma.
Comprehensive Analysis of HMCN1 Somatic Mutation in Clear Cell Renal Cell Carcinoma.
复制标题
作者：
背景资料：肾细胞癌（renal cell carcinoma，RCC）是泌尿生殖系统常见的恶性肿瘤，其中透明细胞肾细胞癌（clear cell renal cell carcinoma，ccRCC）是最具代表性的亚型。近年来，ccRCC的发病率和死亡率逐渐上升;然而，发病机制和潜在的生物标志物仍不清楚。本研究的目的是寻找与肾细胞癌体细胞突变相关的预后基因，并探讨肾细胞癌HMCN 1基因突变的可能机制。方法：从TCGA和cBioPortal获得两个ccRCC队列的体细胞突变数据。提取两个数据集中频繁突变的基因，从中肿瘤突变负荷和生存分析揭示了三个预后基因。进一步对HMCN 1突变进行综合分析，以鉴定差异表达基因并应用功能注释。并对HMCN 1突变与肿瘤免疫的相关性进行了评价。结果：HMCN 1、SYNE 1和BAP 1突变与ccRCC的肿瘤突变负荷和临床预后相关。基因富集分析表明，HMCN 1突变的生物过程和途径与能量代谢的影响。HMCN 1突变与抗肿瘤免疫相关。目前的计算研究在样本量和队列可用性方面存在一些限制。结论：提示HMCN 1基因突变可能通过调节肾细胞代谢和免疫微环境，对肾细胞癌的发生发展具有重要的临床意义。
Background: Renal cell carcinoma (RCC) is a common malignancy of the genitourinary system and clear cell renal cell carcinoma (ccRCC) is the most representative subtype. The morbidity and mortality of ccRCC have gradually risen during recent years; however, the pathogenesis and potential biomarkers remain unclear. The purpose of our study was to find out prognostic genes correlated with somatic mutation and the underlying mechanisms of HMCN1 mutation in ccRCC. Methods: Somatic mutation data of two ccRCC cohorts were acquired from TCGA and cBioPortal. Genes frequently mutated in both datasets were extracted, from which tumor mutation burden and survival analysis revealed three prognostic genes. Further comprehensive analysis of HMCN1 mutation was carried out to identify differentially expressed genes and apply functional annotations. The correlation of HMCN1 mutation and tumor immunity was also evaluated. Results: HMCN1, SYNE1, and BAP1 mutations were associated with both tumor mutation burden and clinical prognosis in ccRCC. Gene enrichment analysis suggested the effects of HMCN1 mutation on biological processes and pathways linked to energy metabolism. HMCN1 mutation was also correlated with anti-tumor immunity. There were several limitations in the sample size and cohort availability of the present computational study. Conclusions: The present results inferred that HMCN1 mutation might have an important clinical significance for ccRCC patients by regulating metabolism and the immune microenvironment.
登录
查看更多内容
DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
50.3
作者：
Jardim DL;Goodman A;de Melo Gagliato D;Kurzrock R
通讯作者：
Kurzrock R
影响因子：
20.3
作者：
Jitschin, Regina;Braun, Martina;Mougiakakos, Dimitrios
通讯作者：
Mougiakakos, Dimitrios
影响因子：
23.4
作者：
Albiges, Laurence;Powles, Tom;Bex, Axel
通讯作者：
Bex, Axel
影响因子：
13.6
作者：
DeBerardinis RJ;Chandel NS
通讯作者：
Chandel NS