血清miR-141和miR-195-5p在乳腺癌早期诊断中的临床意义

 目的 观察血清miR-141和miR-195-5p在乳腺癌早期诊断中的临床意义。方法 选择2015年1月至2018年6月在复旦大学附属华山医院经病理确诊的乳腺癌患者126例，作为乳腺癌组；选择同期在我院活组织检测为乳房良性病变的患者和健康体检者，分别作为良性病变组（75例）和对照组（45例）。用qRT-PCR法检测各组血清miR-141和miR-195-5p水平。并用miR-141和miR-195-5p质粒转染到人乳腺癌细胞MX-1中，观察其增殖和迁移能力。观察各组血清miR-141和miR-195-5p水平变化，乳腺癌患者术后血清miR-141和miR-195-5p水平变化，乳腺癌患者血清miR-141和miR-195-5p水平与临床指标的相关性，及其诊断乳腺癌的灵敏度和特异性。结果 乳腺癌组血清miR-141水平显著高于良性病变组和健康对照组（P<0.01），良性病变组血清miR-141水平高于健康对照组（P<0.01）；乳腺癌组血清miR-195-5p水平明显低于良性病变组和健康对照组（P<0.01），良性病变组血清miR-195-5p水平较健康对照组明显降低（P<0.01），手术后乳腺癌组和乳腺良性病变组血清miR-141水平较手术前明显降低（P<0.01），而miR-195-5p水平较手术前明显升高（P<0.01）。乳腺癌患者血清miR-141和miR-195-5p水平与年龄和肿瘤直径无明显相关性，而与淋巴结转移、雌激素受体（estrogen receptor，ER）、孕激素受体（progesteron receptor，PR）、人类表皮因子受体2（human epidermal growth factor receptor 2，HER-2）、TNM分期、分子分型和组织分型有明显相关性（P<0.01），多元线性回归分析显示血清miR-141和miR-195-5p表达水平与淋巴结转移、PR、TNM分期和分子分型呈线性相关（P<0.05）。MX-1细胞转染miR-141和miR-195-5p质粒后，miR-141促进MX-1细胞的增殖和迁移能力（P<0.01），而miR-195-5p抑制MX-1细胞的增殖和迁移能力（P<0.01）。在乳腺癌诊断方面，联合检测的灵敏度为88.1%，特异性为92.0%，AUC为0.964，明显优于单个指标miR-141（Z=3.413，P<0.01）和miR-195-5p（Z=3.426，P<0.01），而血清miR-141和miR-195-5p的AUC相比较差异无统计学意义。结论 miR-141和miR-195-5p参与乳腺癌疾病的发生发展过程，与乳腺癌细胞增殖和迁移密切相关，在乳腺癌早期诊断中具有重要的临床意义。

Clinical significance of serum miR-141 and miR-195-5p in early diagnosis of breast cancer

Objective To observe the clinical significance of serum miR-141 and miR-195-5p in early diagnosis of breast cancer. Methods From Jan.2015 to Jun.2018,126 patients with breast cancer diagnosed by pathology in Huashan Hospital,Fudan University were selected as breast cancer group.In addtion,75 patients diagnosed as benign breast lesions and 45 healthy people were selected as benign lesions group and control group.The serum miR-141 and miR-195-5p levels were measured by qRT-PCR.The human breast cancer cells (MX-1) were transfected with miR-141 and miR-195-5pplasmids to observe their proliferation and migration ability.The levels of serum miR-141 and miR-195-5p were observed in each group.The correlation amongthe levels of serum miR-141 and miR-195-5p in breast cancer and clinical indexes,and the sensitivity and specificity of those levels were also observed in diagnosis of breast cancer. Results The serum miR-141 levels in breast cancer group were significantly higher than those in benign lesion group and healthy control group (P<0.01),and those levels of benign lesion group were higher than healthy control group (P<0.01).The serum miR-195-5p levels in breast cancer group were significantly lower than those in benign lesion group and healthy control group (P<0.01),those levels of benign lesion group were significantly lower compared with healthy control group (P<0.01).The serum miR-141 levels in patients with breast cancer and benign breast lesion after operation were significantly lower than those before operation (P<0.01),while miR-195-5p levels were significantly higher compared with before surgery (P<0.01).The levels of serum miR-141 and miR-195-5p had no correlation with age and tumor diameter in breast cancer patients,but had significant correlation with lymph node metastasis,estrogen receptor (ER),progesteron receptor (PR),human epidermal growth factor receptor 2 (HER-2),TNM staging,molecular typing and tissue typing (P<0.01),the expression levels of serum miR-141 and miR-195-5p were linearly correlated with lymph node metastasis,PR,TNM staging and molecular typing by multiple linear regression (P<0.05).After miR-141 and miR-195-5p plasmids were transfected into MX-1 cells,miR-141 promoted the proliferation and migration of MX-1 cells (P<0.01),while miR-195-5p inhibited the proliferation and migration of MX-1 cells (P<0.01).In the diagnosis of breast cancer,the sensitivity of combined detection was 88.1%,the specificity was 92.0%,and the AUC was 0.964,it was significantly better than that of miR-141 (Z=3.413,P<0.01) and miR-195-5p (Z=3.426,P<0.01),and there was no significant difference in the area under the curve between serum miR-141 and miR-195-5p. Conclusions miR-141 and miR-195-5p are involved in the development of breast cancer,and are closely related to breast cancer cell proliferation and migration.It has important clinical significance in the diagnosis of early breast cancer.