血清microRNA-186-5p、microRNA-328-5p表达和乳腺癌患者临床病理特征与新辅助化疗效果的关系

Relationship of serum microRNA-186-5p and microRNA-328-5p expression with clinical characteristics and efficacy of neoadjuvant chemotherapy in breast cancer patients

摘要:

目的 探讨血清microRNA-186-5p（miR-186-5p）、microRNA-328-5p（miR-328-5p）表达和乳腺癌患者临床病理特征与新辅助化疗效果的关系。方法 选取2019年2月—2022年2月广西壮族自治区妇幼保健院收治的乳腺癌患者105例作为乳腺癌组，另随机选取该院与乳腺癌患者年龄相匹配的57例健康体检女性作为对照组。乳腺癌患者均接受新辅助化疗，根据化疗反应分为耐药组（30例）和敏感组（75例）。qRT-PCR检测血清miR-186-5p、miR-328-5p表达，比较不同临床病理特征乳腺癌患者血清miR-186-5p、miR-328-5p表达的差异，比较耐药组和敏感组血清miR-186-5p、miR-328-5p表达的差异。多因素Logistic逐步回归分析影响乳腺癌患者新辅助化疗效果的因素。绘制受试者工作特征（ROC）曲线，分析miR-186-5p、miR-328-5p预测乳腺癌患者对新辅助化疗效果的价值。结果 乳腺癌组血清miR-186-5p、miR-328-5p mRNA相对表达量低于对照组（P <0.05）。T₃、T₄期、N_1～3期、HER2阳性乳腺癌患者血清miR-186-5p、miR-328-5p mRNA相对表达量低于T₂期、N₀期、HER2阴性乳腺癌患者（P <0.05）。耐药组血清miR-186-5p、miR-328-5p mRNA相对表达量低于敏感组（P <0.05），T₃、T₄期、N_1～3期占比高于敏感组（P <0.05）。N分期［O^R=3.497（95% CI：1.737，7.041）］、miR-186-5p［O^R=1.680（95% CI：1.169，2.415）］、miR-328-5p［O^R=1.519（95% CI：1.134，2.034）］是影响乳腺癌患者新辅助化疗耐药的危险因素（P <0.05）。ROC曲线分析结果显示，miR-186-5p、miR-328-5p及两者联合预测乳腺癌患者新辅助化疗效果的敏感性分别为76.67%（95% CI：0.553，0.856）、70.00%（95% CI：0.510，0.808）、90.00%（95% CI：0.768，0.977），特异性分别为74.67%（95% CI：0.528，0.831）、76.00%（95% CI：0.544，0.840）、90.67%（95% CI：0.776，0.984）。结论 乳腺癌患者血清miR-186-5p、miR-328-5p表达下调，可能与乳腺癌患者临床病理特征及化疗耐药有关，均可作为新辅助化疗疗效评估的标志物。

Abstract:

Objective To investigate the relationship of serum microRNA-186-5p (miR-186-5p) and microRNA-328-5p (miR-328-5p) expression with clinical characteristics and response to neoadjuvant chemotherapy in breast cancer patients.Methods One hundred and five breast cancer patients (breast cancer group) and 57 healthy volunteers (control group) admitted to our hospital from February 2019 to February 2022 were selected. All breast cancer patients received neoadjuvant chemotherapy and were divided into resistant group (n = 30) and sensitive group (n = 75) according to the response to chemotherapy. Venous blood samples were collected from breast cancer patients before chemotherapy (on the physical examination day of the control group) to detect the expression of serum miR-186-5p and miR-328-5p, and the expression differences of serum miR-186-5p and miR-328-5p in breast cancer patients with different clinical characteristics and chemotherapy response were compared. Stepwise multivariate logistic regression analysis was used to analyze the factors of neoadjuvant chemotherapy efficacy in breast cancer patients, and the receiver operating characteristic curve (ROC) was used to analyze the value of miR-186-5p and miR-328-5p in predicting the response of breast cancer to neoadjuvant chemotherapy.Results The expression of serum miR-186-5p and miR-328-5p of breast cancer group was lower than that of control group (P < 0.05). The expression of serum miR-186-5p and miR-328-5p in breast cancer patients with stage T₃, T₄ N_1~3 and HER2-positive was lower than that in breast cancer patients with stage T₂, N₀ and HER2-negative (P < 0.05). The expression of miR-186-5p and miR-328-5p in the resistant group was lower than that in the sensitive group,and the proportion of stage T_3~4 and stage N_1~3 was higher than that of sensitive group (P < 0.05). Stage N_1~3 [O^R = 3.497 (95% CI: 1.737, 7.041) ], high expression of miR-186-5p [O^R = 1.680 (95% CI: 1.169, 2.415) ], and high expression of miR-328-5p [O^R = 1.519 (95% CI: 1.134, 2.034) ] were risk factors for neoadjuvant chemotherapy resistance in breast cancer patients (P < 0.05). ROC curve results showed that the sensitivity of miR-186-5p, miR-328-5p, and their combination to predict neoadjuvant chemotherapy response in breast cancer patients were 76.67% (95% CI: 0.553, 0.856), 70.00% (95% CI: 0.510, 0.808), 90.00% (95% CI: 0.768, 0.977), and the specificity were 74.67% (95% CI: 0.528, 0.831), 76.00% (95% CI: 0.544, 0.840), 90.67% (95% CI: 0.776, 0.984), respectively.Conclusions The down-regulation of serum miR-186-5p and miR-328-5p in breast cancer patients may be related to clinicopathological characteristics and chemotherapy resistance of breast cancer patients, which can be used as markers to evaluate the efficacy of neoadjuvant chemotherapy.