Hwang Jia, Kim Heeeun, Han Jinseon, Lee Jieun, Hong Sunghoo, Kim Saewoong, Yoon Sungjoo Kim, Choi Keonwoo, Yang Jihoon, Park Unsang, Kim Kwangjoong, Yim Kwangil, Kim Yuil, Choi Yeongjin
Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Department of Urology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
J Pers Med. 2022 Jan 14;12(1):113. doi: 10.3390/jpm12010113.
Although mutations are associated with carcinogenesis, little is known about survival-specific genes in clear cell renal cell carcinoma (ccRCC). We developed a customized next-generation sequencing (NGS) gene panel with 156 genes. The purpose of this study was to investigate whether the survival-specific genes we found were present in Korean ccRCC patients, and their association with clinicopathological findings.
DNA was extracted from the formalin-fixed, paraffin-embedded tissue of 22 ccRCC patients. NGS was performed using our survival-specific gene panel with an Illumina MiSeq. We analyzed NGS data and the correlations between mutations and clinicopathological findings and also compared them with data from the Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) and Renal Cell Cancer-European Union (RECA-EU).
We found a total of 100 mutations in 37 of the 156 genes (23.7%) in 22 ccRCC patients. Of the 37 mutated genes, 11 were identified as clinicopathologically significant. Six were novel survival-specific genes (, , , , , and ), and five were top-ranked mutated genes (, , , , and ). Only was validated as an overall survival-specific gene in this Korean study ( = 0.04, = -0.441), TCGA-KIRC cohort ( = 0.0003), RECA-EU ( = 0.0005). The 10 remaining gene mutations were associated with clinicopathological findings; disease-free survival, mortality, nuclear grade, sarcomatoid component, N-stage, sex, and tumor size.
We discovered 11 survival-specific genes in ccRCC using data from TCGA-KIRC, RECA-EU, and Korean patients. We are the first to find a correlation between CARD6 and overall survival in ccRCC. The 11 genes, including , , , and , could be useful diagnostic, prognostic, and therapeutic markers in ccRCC.
虽然突变与癌症发生相关，但对于透明细胞肾细胞癌（ccRCC）中与生存相关的基因知之甚少。我们开发了一个包含156个基因的定制下一代测序（NGS）基因面板。本研究的目的是调查我们发现的与生存相关的基因是否存在于韩国ccRCC患者中，以及它们与临床病理特征的关联。
从22例ccRCC患者的福尔马林固定、石蜡包埋组织中提取DNA。使用我们的与生存相关的基因面板和Illumina MiSeq进行NGS。我们分析了NGS数据以及突变与临床病理特征之间的相关性，并将它们与癌症基因组图谱-肾透明细胞癌（TCGA-KIRC）和肾细胞癌-欧盟（RECA-EU）的数据进行比较。
我们在22例ccRCC患者的156个基因中的37个基因（23.7%）中总共发现了100个突变。在这37个突变基因中，有11个被确定为具有临床病理意义。6个是新发现的与生存相关的基因（ 、 、 、 、 和 ），5个是排名靠前的突变基因（ 、 、 、 和 ）。在这项韩国研究中，只有 被验证为一个与总生存相关的基因（ = 0.04， = -0.441），在TCGA-KIRC队列中（ = 0.0003），在RECA-EU中（ = 0.0005）。其余10个基因突变与临床病理特征相关；无病生存、死亡率、核分级、肉瘤样成分、N分期、性别和肿瘤大小。
我们利用来自TCGA-KIRC、RECA-EU和韩国患者的数据在ccRCC中发现了11个与生存相关的基因。我们是第一个发现CARD6与ccRCC总生存之间存在相关性的。包括 、 、 和 在内的这11个基因可能是ccRCC中有用的诊断、预后和治疗标志物。
