KCNC3在胃癌组织中表达的临床意义及与患者预后的关系

Clinical significance of KCNC3 expression in gastric cancer and its relationship with prognosis

目的观察胃癌组织中钾电压门控通道亚家族C成员3(KCNC3)的表达状况,分析其临床意义及涉及的相关信号通路。方法应用生物信息学方法对癌症基因组图谱(TCGA)数据库中胃癌的高通量测序数据进行分析,探讨KCNC3 mRNA在胃癌组织表达和预后的关系以及相关信号通路;用Western印迹法检测胃癌细胞系中KCNC3蛋白表达差异;胃癌组织芯片218例胃癌[男165例,女53例,年龄(62.8±11.2)岁]和119例对照无癌胃黏膜组织经免疫组化染色方法分析KCNC3蛋白表达与患者临床特征和预后的关系。结果KCNC3 mRNA在胃癌组织中的表达高于良性胃组织中的表达,其表达水平与胃癌临床分期成正相关。Cox回归生存分析显示,胃癌组织中KCNC3高表达(598例)的患者预后不良,与表达低和无表达组(277例)的患者比较差异有统计学意义(HR=1.69,95%CI:1.39~2.05,P<0.001)。预测通过KCNC4与MAZ基因及Notch信号通路、氧化磷酸化、γ氨基丁酸转运和电子运输链相关信号通路促进胃癌进展。KCNC3蛋白表达与mRNA水平一致,KCNC3高表达与淋巴结转移(χ^(2)=9.512,P=0.023),TNM分期(χ^(2)=12.927,P=0.024)具有相关性。多因素分析结果显示,KCNC3高表达(HR=1.911,95%CI:1.198~3.050)、TNM分期晚(HR=1.962,95%CI:1.497~2.572)、术前血癌胚抗原(CEA)水平高(HR=2.007,95%CI:1.268~3.404)是胃癌患者预后相关的风险因素(均P<0.05)。结论在胃癌发展中,KCNC3高表达可作为患者预后差的独立影响因素,可为靶向治疗提供潜在的标志物。

Objective To observe the expression of potassium voltage-gated channel subfamily C member 3(KCNC3)in gastric cancer and analyze its clinical significance with related signal pathways involved.Methods The high-throughput sequencing data of gastric cancer in the Cancer Genome Atlas(TCGA)database was analyzed by bioinformatics methods to reveal the relationship between KCNC3 mRNA expression and patient prognosis as well as related signal pathways.Western blotting was used to detect differences in KCNC3 protein expression in gastric cancer cell lines.Tissue microarray(218 cases of gastric cancer(165 males and 53 females,aged(62.8±11.2)years)and 119 cases of non-cancer gastric mucosal tissues)was used to detect the relationship between KCNC3 protein expression and clinical characteristics together with patient prognosis statistics analysis followed by immunohistochemical staining.Results KCNC3 mRNA expression was higher in benign gastric tissues,and its expression level was positively correlated with gastric cancer stage.High KCNC3 expression in cancerous tissue indicated poor prognosis(HR=1.69,95%CI:1.39-2.05,P<0.001).KCNC4 and MAZ genes and Notch signaling pathway,oxidative phosphorylation,γ-aminobutyric acid transport and electron transport chain related signaling pathway were predicted to involved in promoting cancer progression.KCNC3 protein expression was in consistent with its mRNA expression level,and high-expressed KCNC3(χ^(2)=9.512,P=0.023)was related to lymph node metastasis and late TNM stage(χ^(2)=12.927,P=0.024).Multivariate analysis showed that high KCNC3 expression(HR=1.911,95%CI:1.198-3.050),late TNM stage(HR=1.962,95%CI:1.497-2.572),and high preoperative blood CEA levels(HR=2.007,95%CI:1.268~3.404)were independent prognosis factors of gastric cancer patients(P<0.05).Conclusion In the development of gastric cancer,high-expressed KCNC3 can be an independent factor for poor patient prognosis and a potential marker for targeted therapy.