KDM6A突变及表达对胃癌预后的影响

KDM6A mutation and expression in gastric cancer are associated with prognosis

目的探讨KDM6A突变或表达与胃癌临床病理特征的关系及其对胃癌患者预后的影响。方法通过二代测序对57例胃癌组织进行全外显子测序,以及Cbioportal、Kaplan Meier-Plotter和the Human Protein Atlas等生物信息数据库资料,分析KDM6A突变与胃癌临床病理特征和胃癌患者总生存时间的关系。结果57例胃癌样本中,KDM6A突变14例,突变率为24.6%。突变组与未突变组比较,Borrmann分型、T分期、TNM分期和肿瘤直径差异有统计学意义(均P<0.05),突变组患者的中位生存时间(53.5个月)短于未突变组(72.0个月,P=0.007)。Kaplan Meier-Plotter数据库的875例胃癌患者中,KDM6A低表达者655例,高表达者220例,低表达患者的中位生存时间(23.5个月)短于高表达患者(30.8个月,P=0.002)。在男性、Ⅲ期、肠型、弥漫型、单纯手术治疗和含氟尿嘧啶方案化疗的患者中,KDM6A表达与患者的总生存时间有关(均P<0.05)。Cbioportal数据库的1172例胃癌患者中,KDM6A突变者70例,未突变者1100例,突变患者的总生存时间(28.9个月)短于未突变患者(35.9个月,P<0.001)。the Human Protein Atlas数据库的355例胃癌患者中,KDM6A高表达97例,KDM6A低表达258例,低表达患者的中位生存时间(13.7个月)短于高表达患者(19.8个月,P=0.022)。结论KDM6A突变、低表达胃癌患者的生存时间更短,且与临床病理因素相关,有可能成为胃癌诊断及治疗的潜在靶点。

Objective To investigate the relationship between KDM6A mutation or expression and clinicopathological characteristics of gastric cancer.Methods Fifty-seven cases of gastric cancer tissues were analyzed by second-generation sequencing,and bioinformation database such as Cbioportal,Kaplan Meier-Plotter,and the Human Protein Atlas were used to analyze the relationship between KDM6A mutation and clinicopathological characteristics of gastric cancer.Results Among 57 gastric cancer samples,14 were KDM6A mutation,and the mutation proportion was 24.6%.Compared with the non-mutation group,the Borrmann classification,T stage,TNM stage and tumor diameter of KDM6A mutant group were significantly different(all P<0.05).The median survival time of the KDM6A mutant patients was 53.5 months,significantly shorter than 72.0 months of the KDM6A non-mutation patients(P=0.007).The analysis result of Kaplan Meier-Plotter database showed that,among all of the 875 patients,655 patients had low KDM6A expression and 220 patients had high expression.The median survival time of patients with low expression was 23.5 months,significantly shorter than 30.8 months of patients with high expression(P=0.002).In male,gastric cancer patients with stageⅢ,intestinal type,diffuse type,simple surgical treatment and fluorouracil chemotherapy,the expression of KDM6A is related to the patient's overall survival time(all P<0.05).The analysis result of Cbioportal database showed that,among all of the 1172 gastric cancer patients,70 patients with KDM6A mutation,1100 patients with non-mutation.The median overall survival time of mutant patients was 28.9 months,significantly shorter than 35.9 months of non-mutation patients(P<0.001).The analysis result of Human Protein Atlas database showed that,among all of the 355 gastric cancer patients,97 patients had high KDM6A expression and 258 patients had low KDM6A expression.The median survival time of patients with low expression was 13.7 months,significantly shorter than 19.8 months of patients with high expression(P=0.022).Conclusions The survival time of gastric cancer patients with KDM6A mutation or low expression is shorter.The mutation and expression of KDM6A are related to clinical pathological factors,which may become a potential target for the diagnosis and treatment of gastric cancer.