SOX17在非小细胞肺癌组织中的表达及临床意义

Expression and clinical significance of SOX17 in non-small cell lung cancer

目的探讨非小细胞肺癌(NSCLC)组织中SOX17的表达及其与临床病理特征和预后的关系。方法采用实时荧光定量PCR(QPCR)法检测2014年1月至2016年12月经手术切除的35例NSCLC组织及10例对应癌旁组织中SOX17 mRNA的水平;免疫组化法检测2001年1月至2006年4月有随访资料的98例NSCLC组织中SOX17蛋白的表达情况,分析SOX17表达与NSCLC临床病理特征和总生存期(OS)的关系;提取癌症基因组图集(TCGA)数据库中SOX17在NSCLC组织中表达的相关数据进行整合,采用Kaplan-Meier Plotter在线数据库分析SOX17表达与OS的关系。结果 QPCR结果显示,SOX17 mRNA在NSCLC组织中的表达量为0. 87±0. 38,低于癌旁组织的1. 90±0. 40(P<0. 01)。TCGA中肺癌队列的高通量RNA测序结果显示,SOX17 mRNA在NSCLC组织中的表达量为4. 85±1. 13,低于癌旁组织的7. 96±1. 01(P<0. 01)。免疫组化检测显示,98例NSCLC组织中SOX17蛋白高表达28例(28. 6%),低表达70例(71. 4%),差异有统计学意义(P<0. 05)。SOX17表达与临床分期和肿瘤大小有关(P<0. 05),而与性别、年龄、淋巴结转移和病理类型无关(P> 0. 05)。生存分析显示,98例患者中SOX17高表达患者的中位OS大于96. 0个月,高于低表达者的67. 0个月(P<0. 05); 77例腺癌患者中SOX17高表达者的中位OS大于96. 0个月,高于低表达者的57. 0个月(P<0. 05),而21例鳞癌患者中SOX17高表达和低表达患者的中位OS分别为54. 0个月和57. 0个月(P>0. 05)。公共数据库生存分析显示,SOX17高表达患者的中位OS为131. 0个月,高于低表达患者的54. 0个月(P<0. 01); 673例肺腺癌患者中SOX17高表达者的中位OS为162. 0个月,高于低表达者的71. 0个月(P<0. 01); 271例肺鳞癌患者中SOX17高表达者和低表达者的中位OS分别为59. 0个月和53. 0个月(P>0. 05)。结论在NSCLC组织中SOX17的mRNA和蛋白呈低表达状态,SOX17表达与临床分期和肿瘤大小有关,SOX17高表达者的预后较好。

Objective To investigate the expression of SOX17in non-small cell lung cancer(NSCLC)and its relationship with clinicopathological features and prognosis.Methods Real-time fluorescence quantitative PCR(QPCR)was used to detect SRY-box containing gene17(SOX17)mRNA levels in35NSCLC tissues and10adjacent tissues from January2014to December2016.The expression of SOX17protein in98NSCLC tissues from January2001to April2006was detected by immunohistochemistry.The relationship between SOX17expression and clinicopathological features of NSCLC was analyzed.The SOX17data from lung cancer of the Cancer Genome Atlas(TCGA)database were extracted and integrated.The influence of SOX17expression on overall survival(OS)was analyzed by Kaplan-Meier plotter online database.Results QPCR results showed that the expression of SOX17in NSCLC tissues was lower than that in adjacent tissues(0.87±0.38vs.1.90±0.40,P<0.01).The high-throughput RNA sequencing results of the lung cancer cohort in public database TCGA showed that the expression of SOX17in NSCLC tissues was significantly lower than that in adjacent tissues(4.85±1.13vs.7.96±1.01,P<0.01).Immunohistochemistry showed that28cases(28.6%)were overexpressed and70cases(71.4%)were underexpressed in98cases of NSCLC tissues with statistic significance(P<0.05).The expression of SOX17was correlated with clinical stage and tumor size(P<0.05),but not with gender,age,lymph node metastasis and pathological type(P>0.05).Kaplan-Meier survival analysis showed that the median OS of98patients with high SOX17expression was greater than96.0months,higher than67.0months of patients with low SOX17expression(P<0.05).The median OS of77adenocarcinoma patients with high SOX17expression was more than96.0months,higher than57.0months of patients with low SOX17expression(P<0.05).For21squamous cell carcinoma patients,the median OS were54.0months with high SOX17expression and57.0months with low SOX17expression,respectively(P>0.05).The public database Kaplan-Meier plotter analysis showed that the median OS of patients with high SOX17expression was131.0months,significantly better than54.0months of patients with low SOX17expression(P<0.01).The median OS of673lung adenocarcinoma patients with high expression of SOX17was162.0months,higher than71.0months of patients with low expression(P<0.01).For271lung squamous cell carcinoma patients,the median OS of patients with high and low expression were59.0months and53.0months,respectively(P>0.05).Conclusion SOX17is down-regulated in NSCLC tissues both at mRNA and protein levels.A significant correlation is observed between SOX17expression and clinical stage and tumor size.Patients with high SOX17expression have better prognosis.