摘要
目的观察胃癌患者行胃癌根治术前血清miR-92a、miR-130b的表达情况,探讨其与临床病理特征及术后预后的关系。方法胃癌患者146例均行胃癌根治术,术前均给予新辅助化疗(顺铂+氟尿嘧啶);同期胃良性病变患者72例,体检健康者40例。采用实时荧光定量PCR法检测胃癌患者术前、胃良性病变患者及体检健康者血清miR-92a、miR-130b相对表达量。比较不同临床分期、浸润深度、有无淋巴结转移等病理特征的胃癌患者术前血清miR-92a、miR-130b相对表达量。146例胃癌患者根据术前血清miR-92a、miR-130b相对表达量均值分为miR-92a高表达组(miR-92a相对表达量≥5.13)72例和miR-92a低表达组(miR-92a相对表达量<5.13)74例、miR-130b高表达组(miR-130b相对表达量≥6.10)75例和miR-130b低表达组(miR-130b相对表达量<6.10)71例;随访3年,采用Kaplan-Meier生存曲线分析miR-92a与miR-130b高、低表达组患者术后3年总生存率。采用多因素Cox回归分析胃癌患者胃癌根治术后预后不良的影响因素。绘制ROC曲线,评估术前血清miR-92a、miR-130b相对表达量预测胃癌患者胃癌根治术后预后不良的效能。结果胃癌患者术前血清miR-92a(5.13±1.43)、miR-130b(6.10±1.51)相对表达量均高于胃良性病变患者(1.06±0.44、1.13±0.45)、体检健康者(0.95±0.33、1.01±0.34)(P<0.05),胃良性病变患者与体检健康者比较差异无统计学意义(P>0.05);临床分期Ⅲ~Ⅳ期、浸润深度T;~T;、有淋巴结转移的胃癌患者血清miR-92a(7.73±1.62、7.13±1.57、7.12±1.56)、miR-130b(8.56±1.68、8.23±1.55、8.59±1.62)相对表达量分别高于临床分期Ⅰ~Ⅱ期(4.01±1.32、5.04±1.36)、浸润深度T;~T;(4.24±1.31、5.15±1.37)、无淋巴结转移者(4.29±1.35、4.92±1.30)(P<0.05)。miR-92a高表达组术后3年总生存率(41.7%)低于miR-92a低表达组(75.7%)(χ^(2)=6.120,P<0.001);miR-130b高表达组术后3年总生存率(42.7%)低于低表达组(76.1%)(χ^(2)=6.236,P<0.001)。术前血清miR-92a相对表达量≥5.13(HR=2.307,95%CI:1.553~2.989,P=0.025)、miR-130b相对表达量≥6.10(HR=3.167,95%CI:1.853~3.852,P=0.012)、临床分期Ⅲ~Ⅳ期(HR=2.223,95%CI:1.264~2.482,P=0.036)、有淋巴结转移(HR=3.736,95%CI:1.955~4.492,P=0.004)是胃癌患者胃癌根治术后预后不良的危险因素。术前血清miR-92a、miR-130b相对表达量的最佳截断值分别为5.22、6.34时,单独及联合检测预测胃癌患者胃癌根治术后预后不良的AUC分别为0.782(95%CI:0.599~0.945,P<0.001)、0.845(95%CI:0.817~0.912,P<0.001)、0.936(95%CI:0.874~0.953,P<0.001),灵敏度分别为71.8%、82.7%、89.2%,特异度分别为86.8%、85.0%、85.5%,二者联合检测预测胃癌患者胃癌根治术后预后不良的AUC大于miR-92a、miR-130b单独检测(Z=3.857,P<0.001;Z=5.206,P<0.001)。结论胃癌患者血清miR-92a、miR-130b表达上调,术前血清miR-92a相对表达量≥5.13、miR-130b相对表达量≥6.10的胃癌患者胃癌根治术后可能预后不良,二者联合检测对胃癌根治术后患者的预后有较高预测价值。
Objective To observe the expressions of serum miR-92aand miR-130band to investigate their relationships with clinicopathological features and prognosis of patients with gastric cancer.Methods Totally 146patients with gastric cancer underwent radical gastrectomy,and were given neoadjuvant chemotherapy (cisplatin+fluorouracil)before operation.Seventy-two patients with benign gastric lesions and 40 healthy volunteers during the same period were enrolled.The relative expressions of serum miR-92aand miR-130bwere detected by real-time fluorescence quantitative PCR.The preoperative relative expressions of serum miR-92aand miR-130bwere compared between patients in different clinical stages,depths of invasion and with and without lymph node metastasis.The patients were divided into 72patients with miR-92a≥5.13 (highly-expressed miR-92agroup)and 74patients with miR-92a<5.13(lowly-expressed miR-92a group),as well as into 75patients with miR-130b ≥6.10 (highly-expressed miR-130bgroup)and 71patients with miR-130b <6.10 (lowly-expressed miR-130bgroup).All patients were followed up for 3years,and Kaplan-Meier survival analysis was done to assess the 3-year overall survival rates in highly-and lowly-expressed miR-92aand miR-130b groups.Multivariate Cox regression was used to analyze the risk factors of poor prognosis after radical gastrectomy for gastric cancer.ROC curve was drawn to evaluate the efficiencies of miR-92aand miR-130bon predicting the poor prognosis of gastric cancer patients.Results The preoperative relative expressions of serum miR-92aand miR-130bwere higher in gastric cancer patients (5.13±1.43,6.10±1.51)than those in patients with benign gastric lesions(1.06±0.44,1.13±0.45)and healthy volunteers(0.95±0.33,1.01±0.34)(P<0.05),and showed no significant differences between the patients with benign gastric lesions and healthy volunteers(P>0.05).The relative expressions of serum miR-92aand miR-130bwere higher in patients in clinical stageⅢ-Ⅳ (7.73±1.62,8.56±1.68),invasion depth of T;-T;(7.13±1.57,8.23±1.55)and lymph node metastasis(7.12±1.56,8.59±1.62)than those in patients with clinical stagesⅠ-Ⅱ (4.01±1.32,5.04±1.36),invasion depth of T;-T;(4.24±1.31,5.15±1.37),and no lymph node metastasis(4.29±1.35,4.92±1.30)(P<0.05).The 3-year overall survival rate was lower in highly-expressed miR-92agroup(41.7%)than that in lowly-expressed miR-92agroup (75.7%)(χ^(2)=6.120,P<0.001),and in highly-expressed miR-130bgroup (42.7%)than that in lowly-expressed miR-130bgroup (76.1%)(χ^(2)=6.236,P<0.001).The preoperative relative expression of miR-92a≥5.13 (HR=2.307,95%CI:1.553-2.989,P=0.025),the relative expression of miR-130b ≥6.10 (HR=3.167,95%CI:1.853-3.852,P=0.012),clinical stage Ⅲ-Ⅳ(HR=2.223,95%CI:1.264-2.482,P=0.036)and lymph node metastasis (HR=3.736,95%CI:1.955-4.492,P=0.004)were the risk factors of poor prognosis of gastric cancer patients.When the optimal cut-off values of the preoperative relative expressions of miR-92aand miR-130b were 5.22and 6.34,the AUCs of single and combined detection of them two for predicting poor prognosis of patients with gastric cancer were 0.782 (95%CI:0.599-0.945,P<0.001),0.845(95%CI:0.817-0.912,P<0.001)and 0.936(95%CI:0.874-0.953,P<0.001),the sensitivities were 71.8%,82.7% and 89.2%,and the specificities were 86.8%,85.0% and 85.5%,respectively.The AUCof combined detection of miR-92aand miR-130bfor predicting poor prognosis of gastric cancer patients was greater than that of single detection (Z=3.857,P<0.001;Z=5.206,P<0.001).Conclusions The expressions of miR-92aand miR-130bare up-regulated in gastric cancer patients.The gastric cancer patients with preoperative relative expression of miR-92a≥5.13and miR-130b≥6.10may have a poor prognosis.The combined detection of miR-92aand miR-130bhas a high predictive value.
作者
魏浩飞
孙海滨
王川
李新江
WEI Hao-fei;SUN Hai-bin;WANG Chuan;LI Xin-jiang(Department of General Surgery,the Second Hospital of Hebei Medical University,Shijiazhuang,Hebei 050000,China)
出处
《中华实用诊断与治疗杂志》
2022年第4期385-389,共5页
Journal of Chinese Practical Diagnosis and Therapy
基金
河北省医学科学研究课题计划项目(20210953)。