微小RNA-21联合磷酸酶和同源盒蛋白D9检测在结直肠癌中的临床价值

Clinical value of microRNA-21 combined with homeobox D9 detection in colorectal cancer

目的探讨微小RNA-21(miR-21)联合同源盒蛋白D9(HOXD9)检测在结直肠癌中的临床价值。方法选择结直肠癌患者(CRC组)及结直肠良性疾病患者(对照组)为研究对象, 采用实时荧光定量聚合酶链反应(RT-qPCR)检测miR-21及HOXD9表达, 比较不同临床病理因素中miR-21及HOXD9的差异。采用ROC曲线分析miR-21联合HOXD9预测结直肠癌1年预后不良的效能。多因素Logistics回归分析结直肠癌死亡的危险因素。Kaplan-Meier法分析miR-21、HOXD9表达与生存期的关系。结果 CRC组结直肠癌患者肿瘤组织miR-21、HOXD9表达均高于癌旁组织和对照组(miR-21分别为0.74±0.08比0.43±0.05、0.44±0.06, HOXD9分别为0.92±0.11比0.57±0.06、0.56±0.07), 差异有统计学意义(F=23.722、18.917, P<0.05)。CRC组低分化、肿瘤最大径≥5 cm、T3~T4、有淋巴结转移及Ⅲ~Ⅳ期患者miR-21、HOXD9表达显著高于中-高分化、肿瘤最大径<5 cm、T1~T2、无淋巴结转移及Ⅰ~Ⅱ期患者。HOXD9联合miR-21预测结直肠癌1年预后不良敏感度、特异度及AUC均高于miR-21、HOXD9、肿瘤分化程度、肿瘤最大径、肿瘤浸润深度、淋巴结转移、TNM分期(敏感度分别0.921比0.824、0.815、0.681、0.667、0.652、0.638、0.644, 特异度分别0.917比0.798、0.769、0.667、0.659、0.673、0.624、0.672, AUC分别0.924比0.801、0.795、0.625、0.658、0.671、0.681、0.701)。Logistics回归分析, 显示miR-21≥0.74、HOXD9≥0.92、为结直肠癌死亡的独立危险因素[β分别为1.477、1.401, 比值比(OR)分别为4.380、4.059, P<0.001]。miR-21≥0.74且HOXD9≥0.92结直肠癌患者中位生存期显著低于其他患者(miR-21<0.74或HOXD9<0.92)[中位生存期(26.3±4.5)个月比(31.2±5.3)个月, Log-rank=13.922, P<0.05]。结论结直肠癌患者HOXD9和miR-21表达显著升高, 两者检测时可显著提高预测结直肠癌预后不良的敏感度及特异度。

Objective To study the clinical value of microRNA-21(miR-21)combined with homeobox D9(HOXD9)detection in colorectal cancer(CRC).Methods Patients with CRC(CRC group)and patients with benign colorectal diseases(control group)were selected as the research subjects.Real-time fluorescent quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of miR-21 and HOXD9,and the expression of miR-21 and HOXD9 in different clinicopathological features was compared.The ROC curve was used to analyze the effectiveness of miR-21 combined with HOXD9 in predicting poor 1-year prognosis of CRC.Multivariate logistic regression analysis of risk factors for colorectal cancer death was carried out.Kaplan-Meier method was used to analyze the relationship between the expression of miR-21 and HOXD9 and survival time.Results The expression levels of miR-21 and HOXD9 in tumor tissues of the CRC group were significantly higher than those in the adjacent tissues and controls(miR-21:0.74±0.08 vs.0.43±0.05,0.44±0.06;HOXD9:0.92±0.11 vs.0.57±0.06,0.56±0.07)(F=23.722,18.917,P<0.05).In the CRC group,the expression of miR-21 and HOXD9 was significantly higher in patients with poorly differentiated tumors,maximum tumor diameter≥5 cm,T3-T4,lymph node metastasis,and stageⅢ-Ⅳthan in patients with moderate-to-high differentiation,maximum tumor diameter<5 cm,T1-T2,and no Lymph node metastasis and stageⅠ-Ⅱ.The sensitivity,specificity and AUC of HOXD9 combined with miR-21 in predicting poor 1-year prognosis of CRC were higher than those of miR-21,HOXD9,tumor differentiation,maximum tumor diameter,tumor infiltration depth,lymph node metastasis,and TNM staging(sensitivity:0.921 vs.0.824,0.815,0.681,0.667,0.652,0.638,0.644;specificity:0.917 vs.0.798,0.769,0.667,0.659,0.673,0.624,0.672;AUC:0.924 vs.0.801,0.795,0.625,0.658,0.671,0.681,0.701).Logistics regression analysis showed that miR-21≥0.74 and HOXD9≥0.92 were independent risk factors for CRC cancer death[β:1.477 and 1.401;odds ratio(OR):4.380 and 4.059,P<0.001].The median survival time of CRC patients with miR-21≥0.74 and HOXD9≥0.92 was significantly shorter than that of other patients(miR-21<0.74 or HOXD 9<0.92)[median survival time:(26.3±4.5)months vs.(31.2±5.3)months,Log-rank=13.922,P<0.05].Conclusion The expression of HOXD9 and miR-21 is significantly increased in patients with CRC,and the combined detection of HOXD9 and miR-21 can significantly improve the sensitivity and specificity in predicting poor prognosis of CRC.