胃镜活检组织SF3B4及miR-96表达在胃癌病情及预后评估中的临床价值

The clinical value of SF3B4 and miR-96 expression in gastroscopy biopsy tissue in the evaluation of gastric cancer condition and prognosis

目的分析胃镜活检组织剪接因子3b亚基4(SF3B4)及微小RNA-96(miR-96)表达在胃癌病情及预后评估中的临床价值。方法选择2017年1—12月湖北省洪湖市人民医院普外科诊治胃癌患者95例为胃癌组,胃良性疾病患者60例为非胃癌组,采用实时荧光定量PCR(RT-qPCR)检测组织SF3B4、miR-96表达,比较不同临床病理资料中SF3B4、miR-96表达的差异;采用ROC曲线分析SF3B4及miR-96预测胃癌1年预后不良的价值;多因素Logistic回归分析胃癌患者死亡的危险因素;Kaplan-Meier法分析SF3B4、miR-96表达与生存期的关系。结果胃癌组肿瘤组织SF3B4、miR-96表达均显著高于癌旁组织、非胃癌组病灶组织(F/P=516.766/<0.001、887.495/<0.001)。胃癌低分化、肿瘤最大直径≥5 cm、T3-4、有淋巴结转移及cTNM分期Ⅲ~Ⅳ期患者SF3B4及miR-96表达显著高于胃癌中-高分化、肿瘤最大直径<5 cm、T1-2、无淋巴结转移及cTNM分期Ⅰ~Ⅱ期患者(SF3B4:t/P=4.151/<0.001、5.695/<0.001、6.561/<0.001、7.943/<0.001、4.629/<0.001;miR-96:t/P=4.543/<0.001、3.692/<0.001、5.061/<0.001、5.842/<0.001、5.109/<0.001)。SF3B4、miR-96及二者联合预测胃癌1年预后不良的AUC分别为0.785、0.779、0.952,二者联合优于各自单独预测效能(Z/P=3.451/0.017、3.565/0.014)。多因素Logistic回归分析显示SF3B4≥1.51、miR-96≥1.28、肿瘤分化程度低分化、肿瘤最大直径≥5 cm、肿瘤浸润深度T3-4、有淋巴结转移、cTNM分期Ⅲ~Ⅳ期为胃癌1年死亡的独立危险因素[OR(95%CI)=4.225(1.034~4.623)、3.877(1.142~6.189)、2.261(1.275~5.726)、2.487(1.338~7.516)、2.088(1.023~5.367)、2.779(1.161~4.591)、3.013(1.416~5.791)]。95例胃癌患者随访至终点时存活36例,死亡59例。SF3B4≥1.51且miR-96≥1.28胃癌患者中位生存期(23.7±5.4)个月低于SF3B4<1.51或miR-96<1.28患者(31.2±6.5)个月(Log-rank=11.457,P<0.001)。结论胃癌患者胃镜活检组织SF3B4和miR-96表达显著升高,与病情严重程度、预后及生存期密切相关,可作为胃癌病情及预后评估的标志物,且二者联合检测时可提高预测胃癌预后不良的敏感度及特异度。

Objective To analyze the clinical value of splicing factor 3b subunit 4(SF3B4)and microRNA-96(miR-96)expression in gastric cancer disease and prognosis evaluation in endoscopic biopsy tissue.Methods Ninety-five gastric cancer patients diagnosed and treated in the General Surgery Department of Honghu People's Hospital in Hubei Province from January to December 2017 were selected as the gastric cancer group,and 60 patients with benign gastric diseases were selected as the non gastric cancer group.Real time fluorescence quantitative PCR(RT qPCR)was used to detect the expression of SF3B4 and miR-96 in tissues,and the differences in SF3B4 and miR-96 expression in different clinical and pathological data were compared;The value of using ROC curve analysis to predict poor 1-year prognosis of gastric cancer using SF3B4 and miR-96;Multivariate logistic regression analysis of risk factors for death in gastric cancer patients;Kaplan Meier method was used to analyze the relationship between SF3B4,miR-96 expression and survival.Results The expression of SF3B4 and miR-96 in tumor tissues of gastric cancer group was significantly higher than that in adjacent tissues and non gastric cancer group lesion tissues(F/P=516.766/<0.001,887.495/<0.001).The expression of SF3B4 and miR-96 in patients with poorly differentiated gastric cancer,maximum tumor diameter≥5 cm,T3-4,lymph node metastasis,and cTNM staging III-IV was significantly higher than that in patients with moderately well differentiated gastric cancer,maximum tumor diameter<5 cm,T1-2 Patients with no lymph node metastasis and cTNM stage I-II(SF3B4:t/P=4.151/<0.001,5.695/<0.001,6.561/<0.001,7.943/<0.001,4.629/<0.001;miR-96:t/P=4.543/<0.001,3.692/<0.001,5.061/<0.001,5.842/<0.001,5.109/<0.001).The AUC of SF3B4,miR-96,and their combination for predicting poor 1-year prognosis in gastric cancer were 0.785,0.779,and 0.952,respectively.The combined predictive efficacy of SF3B4,miR-96,and their combination was superior to their individual predictive efficacy(Z/P=3.451/0.017,3.565/0.014).Multivariate logistic regression analysis showed that SF3B4≥1.51,miR-96≥1.28,poorly differentiated tumor,maximum tumor diameter≥5 cm,depth of tumor infiltration T3-4,presence of lymph node metastasis,and cTNM stage III-IV were independent risk factors for 1-year mortality in gastric cancer[OR(95%CI)=4.225(1.034-4.623),3.877(1.142-6.189),2.261(1.275-5.726),2.487(1.338-7.516),2.088(1.023-5.367)2.779(1.161-4.591),3.013(1.416-5.791)].Among 95 gastric cancer patients,36 survived and 59 died at the endpoint of follow-up.The median survival time of gastric cancer patients with SF3B4≥1.51 and miR-96≥1.28 was(23.7±5.4)months lower than that of SF3B4<1.51 or miR-96<1.28 patients(31.2±6.5)months(Log rank=11.457,P<0.001).Conclusion The expression of SF3B4 and miR-96 in gastric cancer patients undergoing gastroscopy biopsy is significantly increased,which is closely related to the severity,prognosis,and survival of the disease.It can be used as a biomarker for evaluating the condition and prognosis of gastric cancer,and the combined detection of the two can improve the sensitivity and specificity of predicting poor prognosis of gastric cancer.