血清miRNA-128a和miRNA-128b表达对胃癌早期诊断和预后的影响

 目的 观察血清miRNA-128a和miRNA-128b表达在胃癌早期诊断和预后的影响。方法 选择2015年1月至2017年1月在复旦大学附属华山医院就诊且病理确诊的胃癌患者118例，设为胃癌组。选择同期在我院病理诊断为胃息肉者75例和健康体检者45例，分别为胃息肉组和健康对照组。用定量RT-PCR （qRT-PCR）法检测各组血清miRNA-128a和miRNA-128b表达水平。观察胃癌患者血清miRNA-128a和miRNA-128b表达水平与临床病理指标，及其诊断和预测2年内存活率的效能。结果 胃癌组血清miRNA-128a表达水平明显高于胃息肉组（q=26.388，P<0.01）和健康对照组（q=32.195，P<0.01），手术后较术前明显降低（t=14.321，P<0.01），胃息肉组明显高于健康对照组（q=7.198，P<0.01）；而胃癌组血清miRNA-128b表达水平明显低于胃息肉组（q=211.148，P<0.01）和健康对照组（q=249.984，P<0.01），手术后较术前明显升高（t=15.139，P<0.01），胃息肉组明显低于健康对照组（q=38.232，P<0.01）。血清miRNA-128a和miRNA-128b表达水平对诊断胃癌具有较高的灵敏度和特异性，联合检测的灵敏度为78.8%，特异性为97.3%，曲线下面积明显高于单个指标miRNA-128a （Z=3.436，P<0.01）和miRNA-128b （Z=2.658，P<0.01）。胃癌患者血清miRNA-128a和miRNA-128b表达水平与肿瘤细胞分化程度、TNM分期、淋巴结转移和浸润深度具有明显相关性（P<0.01）。病例随访2年，胃癌存活组血清miRNA-128a表达水平明显低于死亡组（P<0.01）；当其>98.47 fmol/L，预测2年内出现死亡的灵敏度为89.5%，特异性为81.8%，曲线面积为0.889。而存活组的血清miRNA-128b表达水平明显高于死亡组（P<0.01），当其≤94.86 fmol/L，预测2年内死亡的灵敏度为94.7%，特异性为81.8%，曲线下面积为0.931。结论 联合检测血清miRNA-128a和miRNA-128b有助于胃癌诊断，对2年内出现死亡的预测具有重要参考价值。

Impact of serum miRNA-128a and miRNA-128b expression on early diagnosis and prognosis in patients with gastric cancer

Objective To observe the impact of serum miRNA-128a and miRNA-128b expression on early diagnosis and prognosis in patients with gastric cancer. Methods One hundred and eighteen patients with gastric cancer diagnosed in Huashan Hospital,Fudan University from Jan.2015 to Jan.2017 were selected as the gastric cancer group.Seventy-five patients with gastric polyps by pathological diagnosis and 45 healthy people were selected as gastric polyps group and healthy control.Quantitative RT-PCR was used to detect the expression levels of serum miRNA-128a and miRNA-128b in each group.The relation among serum miRNA-128a and miRNA-128b levels,clinic pathological parameters in gastric cancer patients and prognosis was observed,and their efficacy of diagnose and predicting death within 2 years was also observed. Results The serum miRNA-128a expression in gastric cancer group was significantly higher than that in gastric polyp group (q=26.388,P<0.01) and healthy control (q=32.195,P<0.01),the expression in gastric polyp group was significantly higher compared with the healthy control (q=7.198,P<0.01),and after operation the expression level was significantly lower than that before operation (t=14.321,P<0.01).The serum miRNA-128b expression in gastric cancer group was significantly lower than that in gastric polyp group (q=211.148,P<0.01) and healthy control group (q=249.984,P<0.01),the expression of those in gastric polyp group was also significantly lower compared healthy control group(q=38.232,P<0.01),and the expression was significantly higher after surgery than before surgery (t=15.139,P<0.01).The serum miRNA-128a and miRNA-128b expression had high sensitivity and specificity in the diagnosis of gastric cancer,the sensitivity of combined detection was 78.8%,the specificity was 97.3%,and the area under curve was significantly higher than miRNA-128a (Z=3.436,P<0.01) and miRNA-128b (Z=2.658,P<0.01).The expression of serum miRNA-128a and miRNA-128b in patients with gastric cancer were significantly correlated with tumor cell differentiation,TNM staging,lymph node metastasis and depth of invasion (P<0.01).After 2 years' follow-up,the serum miRNA-128a expression in survival group was significantly lower than that in death group (P<0.01).When its level was >98.47 fmol/L,the sensitivity of predicting death within 2 years was 89.5%,the specificity was 81.8%,and the curve area was 0.889.The serum miRNA-128b expression in survival group was significantly higher than that in death group (P<0.01),when its level was ≤ 94.86 fmol/L,the sensitivity of predicting death within 2 years was 94.7%,the specificity was 81.8%,and the curve area was 0.931. Conclusions Combined detection of serum miRNA-128a and miRNA-128b is helpful for diagnosis in patients with gastric cancer and has important reference value for predicting death in gastric cancer patients within 2 years.