血清miR-196a-5p和miR-339-5p表达水平在乳腺癌诊断中的应用价值

Application value of serum miR-196a-5p and miR-339-5p expression levels in diagnosis of breast cancer

背景与目的:研究显示,miR-196a-5p在乳腺癌细胞中呈显高表达,而miR-339-5p呈低表达,两者可能是乳腺癌潜在治疗靶点和诊断标志物。因此,本研究探讨血清miR-196a-5p和miR-339-5p表达水平在乳腺癌诊断中的应用价值。方法:选择2016年1月—2017年6月收治的乳腺癌患者107例(乳腺癌组),以及同期诊断为乳腺良性疾病的患者60例(乳腺良性疾病组)和健康体检者35例(健康对照组),比较各组血清miR-196a-5p、miR-339-5p以及乳腺癌特异性标记物CA15-3水平差异,分析三者血清水平对乳腺癌的诊断效能,并分析乳腺癌患者血清miR-196a-5p和miR-339-5p表达水平之间的关系以及两者水平与乳腺癌临床病理特征的关系。结果:在健康对照组、乳腺良性疾病组、乳腺癌组,血清miR-196a-5p与miR-339-5p水平分别依次升高和依次降低,组间差异均有统计学意义(均P<0.01),乳腺癌组血清CA15-3水平明显高于乳腺良性疾病组和健康对照组(均P<0.01),但后两组间差异无统计学意义(P>0.05)。血清miR-196a-5p和miR-339-5p水平诊断乳腺癌的效能均明显优于血清CA15-3(Z=2.543,P<0.05;Z=2.190,P<0.05),而miR-196a-5p与miR-339-5p之间的诊断效能差异无统计学意义(P>0.05);miR-196a-5p与miR-339-5p联合检测诊断乳腺癌的AUC为0.937,灵敏度与特异度分别为91.6%、88.3%,明显优于两者单独检测(miR-196a-5p:Z=3.044,P<0.01;miR-339-5p:Z=3.020,P<0.01)。乳腺癌患者术前血清miR-196a-5p与miR-339-5p表达水平呈负相关(r=-0.764,P<0.01);与术前比较,乳腺癌患者术后血清miR-196a-5p水平明显降低,而miR-339-5p水平明显升高(均P<0.01)。乳腺癌患者血清miR-196a-5p和miR-339-5p水平与肿瘤直径、淋巴结转移和TNM分期明显有关(均P<0.01)。结论:血清miR-196a-5p和miR-339-5p表达水平检测对乳腺癌有较好的诊断价值与潜在的预后监测价值,两者诊断乳腺癌的诊断效能均优于CA15-3,且两者联合检测能够进一步提高对乳腺癌的诊断效能。

Background and Aims:Studies have demonstrated that miR-196a-5p expression is increased while miR-339-5p expression is decreased in breast cancer cells,so they may probably be the therapeutic targets or diagnostic markers for breast cancer.Therefore,this study was conducted to evaluate the application values of serum levels of miR-196a-5p and miR-339-5p in diagnosis of breast cancer.Methods:One hundred and seven patients with breast cancer(breast cancer group)treated during January 2016 to June 2017,along with 60 patients with benign breast disease(benign breast disease group)and 35 individuals undergoing healthy maintenance examination(healthy control group)during the same period were enrolled.The differences of serum levels of miR-196a-5p and miR-339-5p as well as the breast cancer-specific marker CA15-3 were compared among groups,and the diagnostic abilities of serum levels of the three indices were determined.In addition,the relationship between serum levels of miR-196a-5p and miR-339-5p in breast cancer patients as well as the associations of their levels with the clinicopathologic characteristics of breast cancer were also analyzed.Results:In healthy control group,benign breast disease group and breast cancer group,the serum levels of miR-196a-5p and miR-339-5p were successively increased and decreased respectively,and the differences between groups were all statistically significant(all P<0.01).the serum CA15-3 level in breast cancer group was significantly higher than that in benign breast disease group and healthy control group(both P<0.01),but the difference between the latter two groups showed no statistical significance(P>0.05).The diagnostic abilities for breast cancer of both serum miR-196a-5p and miR-339-5p levels were significantly superior to that of serum CA15-3 level(Z=2.543,P<0.05;Z=2.190,P<0.05),but the diagnostic abilities between miR-196a-5p and miR-339-5p showed no significant difference(P>0.05).The AUC of the combined detection of miR-196a-5p and miR-339-5p for diagnosis of breast cancer was 0.937,with the sensitivity and specificity 91.6%and 88.3%respectively,which was significantly superior to that of either lone detection(miR-196a-5p:Z=3.044,P<0.01;miR-339-5p:Z=3.020,P<0.01).There was a negative correlation between the preoperative serum expression levels of miR-196a-5p and miR-339-5p in breast cancer patients(r=–0.764,P<0.01),and serum miR-196a-5p level was decreased while the serum miR-339-5p level was increased significant after surgery compared with those before surgery in breast cancer patients(both P<0.01).The serum levels of both miR-196a-5p and miR-339-5p in breast cancer patients were significantly associated with tumor diameter,lymph node metastasis,and TNM stage(all P<0.01).Conclusion:The determination of serum levels of miR-196a-5p and miR-339-5p has high diagnostic value and also has a potential monitoring value for breast cancer.Both diagnostic abilities of miR-196a-5p and miR-339-5p are superior to that of CA15-3,and their combined detection can further increase the diagnostic efficacy.