血清microRNA-33a-5p在结直肠癌患者中的表达及生存预后的关系研究

Relationship Between Expression of Serum MicroRNA-33a-5p and Survival Prognosis in Patients with Colorectal Cancer

目的检测结直肠癌(CRC)患者血清中microRNA-33a-5p(miR-33a-5p)的相对表达水平,探讨其辅助诊断价值及与生存预后的关系。方法收集CRC 134例、结直肠息肉69例及同期匹配的健康对照69例血清标本,检测所有标本miR-33a-5p的相对含量及CRC患者术后miR-33a-5p的相对含量。分析CRC血清miR-33a-5p的相对表达水平在不同年龄、性别、肿瘤大小、肿瘤位置和临床TNM分期的差异以及与CEA及CA199的相关性。利用二元Logistic回归和ROC曲线评估各项指标的诊断效能,评价其对CRC的辅助诊断价值。Kaplan-Meier及Cox回归分析其在预后中的临床价值。结果CRC组miR-33a-5p的相对含量低于结直肠息肉组和健康对照组,差异有统计学意义(P<0.001);CRC组患者手术前后相比较,差异有统计学意义(P<0.001)。CRC组患者miR-33a-5p的相对含量在肿瘤大小及临床TNM分期,差异有统计学意义(P<0.001)。CRC患者血清中miR-33a-5p的相对含量与CEA及CA199之间无相关性(P>0.05)。CRC组与健康对照组比较,曲线下面积(AUC)为0.805,三者联合AUC达0.831,敏感度达97.8%。miR-33a-5p低表达组的总生存时间明显低于miR-33a-5p高表达组(P<0.05)。单因素分析临床TNM分期及miR-33a-5p表达水平与患者预后相关(P<0.05),Cox回归多因素分析发现临床TNM分期和miR-33a-5p低表达是患者预后的独立危险因素。结论miR-33a-5p在CRC患者血清中低表达,与临床TNM分期有关,其表达水平与CRC的进展与预后有关;miR-33a-5p联合CEA和CA199可提高诊断敏感度,其有望成为筛查CRC的生物学指标。

Objective To detect the relative expression level of microRNA-33a-5p(miR-33a-5p)in serum of patients with colorectal cancer(CRC),and to explore its auxiliary diagnostic value and relationship with survival prognosis.Methods Serum samples were collected from 134 cases of CRC,69 cases of colorectal polyps and 69 matched healthy controls in the same period.The levels of miR-33a-5p in all samples and miR-33a-5p in CRC patients after surgery were detected.The relative expression level of CRC serum miR-33a-5p was analyzed in dfferent age,gender,tumor size,tumor location and clinicopathological stage as well as its correlation with CEA and CA199.Binary Logistic regression and ROC curve were used to evaluate the diagnostic efficacy of each index and evaluate its auxiliary diagnostic value for CRC.Kaplan-Meier and Cox regression were used to analyze its clinical value in prognosis.Results The relative content of miR-33a-5p in CRC group was lower than that in colorectal polyp group and healthy control group,and the difference was statistically significant(P<0.001).Dynamic monitoring of CRC patients before and after operation showed statistically significant difference(P<0.001).The relative content of miR-33a-5p in CRC patients had significant differences in tumor size and clinical TNM stage(P<0.001).There was no correlation between the relative content of miR-33a-5p in CRC serum,CEA and CA199(P>0.05).Compared with healthy controls,the area under the curve(AUC)was 0.805,and the combined AUC was 0.831,the sensitivity was 97.8%.The overall survival time of miR-33a-5p low expression group was significantly lower than that of miR-33a-5p high expression group(P<0.05).Univariate analysis showed that clinical TNM stage and miR-33a-5p expression level were correlated with patient prognosis(P<0.05).Cox regression multivariate analysis found that clinical TNM stage and low miR-33a-5p expression were independent risk factors for patient prognosis.Conclusion The low expression of miR-33a-5p in the serum of CRC patients is related to clinical TNM stage,and its expression level may be related to the progression and prognosis of CRC.miR-33a-5p combined with CEA and CA199 can improve the diagnostic sensitivity,which is expected to be a biological indicator for screening CRC.