PDF(Pubmed)
Abstract：
Although sex differences have been reported in patients with clear cell renal cell carcinoma (ccRCC), biological sex has not received clinical attention and genetic differences between sexes are poorly understood. This study aims to identify sex-specific gene mutations and explore their clinical significance in ccRCC. We used data from The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC), The Renal Cell Cancer-European Union (RECA-EU) and Korean-KIRC. A total of 68 sex-related genes were selected from TCGA-KIRC through machine learning, and 23 sex-specific genes were identified through verification using the three databases. Survival differences according to sex were identified in nine genes (ACSS3, ALG13, ASXL3, BAP1, JADE3, KDM5C, KDM6A, NCOR1P1, and ZNF449). Female-specific survival differences were found in BAP1 in overall survival (OS) (TCGA-KIRC, p = 0.004; RECA-EU, p = 0.002; and Korean-KIRC, p = 0.003) and disease-free survival (DFS) (TCGA-KIRC, p = 0.001 and Korean-KIRC, p = 0.000004), and NCOR1P1 in DFS (TCGA-KIRC, p = 0.046 and RECA-EU, p = 0.00003). Male-specific survival differences were found in ASXL3 (OS, p = 0.017 in TCGA-KIRC; and OS, p = 0.005 in RECA-EU) and KDM5C (OS, p = 0.009 in RECA-EU; and DFS, p = 0.016 in Korean-KIRC). These results suggest that biological sex may be an important predictor and sex-specific tailored treatment may improve patient care in ccRCC.
摘要：
尽管在透明细胞肾细胞癌（ccRCC）患者中有性别差异的报道，生物学性别尚未受到临床关注，对性别之间的遗传差异了解甚少。本研究旨在鉴定性别特异性基因突变并探讨其在ccRCC中的临床意义。我们使用来自癌症基因组图谱-肾肾透明细胞癌（TCGA-KIRC）的数据，肾细胞癌-欧盟（RECA-EU）和韩国-KIRC。通过机器学习从TCGA-KIRC中筛选出68个性别相关基因,通过使用三个数据库进行验证，鉴定出23个性别特异性基因。在9个基因（ACSS3，ALG13，ASXL3，BAP1，JADE3，KDM5C，KDM6A,NCOR1P1和ZNF449)。BAP1在总生存期（OS）中发现了女性特异性生存差异（TCGA-KIRC，p=0.004；RECA-EU，p=0.002；和韩国KIRC，p=0.003）和无病生存率（DFS）（TCGA-KIRC，p=0.001和韩国KIRC，p=0.000004),和DFS中的NCOR1P1(TCGA-KIRC，p=0.046和RECA-EU，p=0.00003)。在ASXL3中发现了男性特异性生存差异(OS，p=0.017inTCGA-KIRC;andOS,RECA-EU中的p=0.005)和KDM5C(操作系统，p=0.009inRECA-EU;andDFS,在韩国-KIRC中p=0.016)。这些结果表明，生物性别可能是重要的预测因素，针对性别的定制治疗可能会改善ccRCC的患者护理。
