乳腺癌组织中miR-199b-5p和MTA1表达水平与临床病理特征和预后的关系

Expression of miR-199b-5p and MTA1 in breast cancer and their correlations with clinicopathological characteristics and prognosis

目的 检测乳腺癌组织中miR-199b-5p与MTA1表达情况,并分析其表达水平与临床病理特征和预后关系。方法 选取2017年10月至2018年10月期间河南大学第一附属医院收治的行乳腺切除手术的乳腺癌患者135例作为研究对象,取其癌组织与癌旁组织分别作为癌旁组织组与乳腺癌组,qRT-PCR法测定癌组织与癌旁组织miR-199b-5p、MTA1 mRNA水平,免疫组化法分析组织MTA1阴阳性,分析miR-199b-5p、MTA1表达与乳腺癌患者年龄、绝经情况(是、否)、肿瘤直径(<2 cm、≥2 cm)、临床分期(Ⅰ~Ⅱ期、Ⅲ期)、分子分型(Lumina A/B型、HER-2阳性型、三阴性型)、淋巴结转移(是、否)关系。结果 与癌旁组织组相比,乳腺癌组癌组织miR-199b-5p水平降低,MTA1 mRNA水平升高(P<0.05);与癌旁组织组相比,乳腺癌组MTA1阳性率升高(P<0.05);乳腺癌患者癌组织miR-199b-5p表达与临床分期、淋巴结转移有关(P<0.05);MTA1表达与临床分期、淋巴结转移、分子分型有关(P<0.05);乳腺癌患者治疗后进行5年随访,miR-199b-5p低表达患者5年内累积生存率(71.8%)低于miR-199b-5p高表达患者(89.1%)(log Rankχ^(2)=6.661,P=0.010);MTA1阳性患者5年内累积生存率(71.6%)低于MTA1阴性患者(90.2%)(log Rankχ^(2)=7.590,P=0.006);单因素COX分析表明,肿瘤直径、临床分期、分子分型、淋巴结转移、miR-199b-5p、MTA1是影响乳腺癌预后不良的危险因素(P<0.05);多因素COX回归分析显示,临床分期、淋巴结转移、miR-199b-5p、MTA1水平是影响乳腺癌预后的危险因素(P<0.05)。结论 乳腺癌患者miR-199b-5p低表达,MTA1 mRNA与阳性率高于癌旁组织,miR-199b-5p低水平、MTA1阳性表达与乳腺癌患者临床病理特征淋巴结转移、肿瘤分期以及患者预后密切相关,两者可能是乳腺癌患者预后不良的预测靶基因。

Objective To detect the expression of miR-199b-5p and MTA1 in breast cancer tissues,and analyze the correlation between their expression levels and clinicopathological characteristics and prognosis.Methods A total of 135 breast cancer patients who underwent mastectomy in the First Affiliated Hospital of Henan University from October 2017 to October 2018 were selected.The cancer tissues and adjacent tissues were taken as breast cancer group and adjacent tissue group,respectively.The levels of miR-199b-5p and MTA1 mRNA in cancer tissues and adjacent tissues were measured by qRT-PCR.Immunohistochemical method was used to analyze the positive and negative of MTA1.The correlations between the expression of miR-199b-5p and MTA1 with age,menopause(yes,no),tumor diameter(<2 cm,≥2 cm),clinical stage(Ⅰ-Ⅱ,Ⅲ),molecular classification(Lumina A/B,HER-2 positive,triple negative),and lymph node metastasis(yes,no)of breast cancer patients were analyzed.Results Compared with the adjacent tissue group,miR-199b-5p levels were decreased,and MTA1 mRNA levels were significantly increased in the breast cancer tissue group(P<0.05).The MTA1 positivity rate was significantly higher in the breast cancer group than in the adjacent tissue group(P<0.05).The expression of miR-199b-5p in breast cancer tissue was significantly associated with clinical stage and lymph node metastasis(P<0.05).MTA1 expression was significantly correlated to clinical stage,lymph node metastasis,and molecular subtypes in breast cancer patients(P<0.05).After a 5-year follow-up,patients with low miR-199b-5p expression had a significantly lower 5-year cumulative survival rate(71.8%)compared to patients with high miR-199b-5p expression(89.1%)(log Rank=6.661,P=0.010).MTA1-positive patients had a lower 5-year cumulative survival rate(71.6%)compared to MTA1-negative patients(90.2%)(log Rank=7.590,P=0.006).Univariate COX analysis showed that tumor diameter,clinical stage,molecular subtype,lymph node metastasis,miR-199b-5p,and MTA1 were risk factors for poor prognosis in breast cancer(P<0.05).Multivariate COX regression analysis revealed that clinical stage,lymph node metastasis,miR-199b-5p,and MTA1 levels were independent risk factors affecting the prognosis of breast cancer(P<0.05).Conclusion Breast cancer patients with low miR-199b-5p expression and high MTA1 mRNA and positivity rate in tumor tissues were associated with lymph node metastasis,tumor stage,and patient prognosis.Both miR-199b-5p and MTA1 may serve as predictive target genes for poor prognosis in breast cancer patients.