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miR-27a-3p及YAP1 mRNA在乳腺癌中的表达及其与临床病理、生存预后的关系分析

Expressions of miR-27a-3p mRNA and YAP1 mRNA in Breast Cancer and the Relationship With Clinicopathology and Survival Prognosis

  • 摘要:
    目的  分析miR-27a-3p及Yes相关蛋白1(Yes-associated protein 1, YAP1) mRNA在乳腺癌中的表达,并探究与临床病理特征以及患者生存预后的关系。
    方法  研究对象为2019年1月–2021年1月在我院接受乳腺切除手术的130例乳腺癌患者,通过qRT-PCR法检测乳腺肿瘤组织及其相邻正常乳腺组织样本中miR-27a-3p和YAP1 mRNA的表达,同时探究二者表达与患者的临床病理特征以及生存预后之间的关系。
    结果  相较于相邻正常乳腺组织,乳腺肿瘤组织中miR-27a-3p mRNA表达较低(P<0.05),YAP1 mRNA表达较高(P<0.05);乳腺肿瘤组织中miR-27a-3p mRNA表达与YAP1 mRNA表达之间存在负相关关系(r=−0.456,P<0.05);miR-27a-3p mRNA表达与乳腺癌患者肿瘤直径、组织学分级、TNM分期、淋巴结转移、脉管侵犯相关(P<0.05),YAP1 mRNA表达与乳腺癌患者组织学分级、TNM分期、淋巴结转移、脉管侵犯相关(P<0.05);Kaplan-Meier生存分析显示,miR-27a-3p低表达组3年总生存率为71.60%(48/67),低于miR-27a-3p高表达组的91.50%(54/59)(log-rank χ2=8.211,P=0.004),YAP1高表达组3年总生存率为73.80%(45/61),低于YAP1低表达组的87.70%(57/65)(log-rank χ2=4.429,P=0.035);多因素回归分析显示,淋巴结转移〔风险比(hazard ratio, HR)=1.409,95%置信区间(confidence interval, CI):1.057~1.644,P=0.046〕、脉管侵犯(HR=1.541,95%CI:1.076~1.869,P=0.045)、miR-27a-3p mRNA低表达(HR=0.593,95%CI:0.388~0.925,P=0.018)、YAP1 mRNA高表达(HR=0.628,95%CI:0.405~0.912,P=0.022)是影响乳腺癌患者3年总生存率的相关因素。
    结论  乳腺肿瘤组织中miR-27a-3p mRNA呈明显低表达,YAP1 mRNA呈明显高表达,miR-27a-3p mRNA低表达及YAP1 mRNA高表达与不良临床病理特征、生存预后有关,是影响乳腺癌患者3年总生存率的危险因素,有望作为治疗乳腺癌的新的潜在靶点。

     

    Abstract:
    Objective  To analyze the expression levels of miR-27a-3p mRNA and Yes-associated protein 1 (YAP1) mRNA in breast cancer, and to explore their relationships with clinicopathological features and the survival prognosis of patients.
    Methods A total of 130 breast cancer patients who underwent mastectomy in our hospital between January 2019 and January 2021 were enrolled. The expression levels of miR-27a-3p and YAP1 mRNA in breast tumor tissues and adjacent normal breast tissues were assessed by qRT-PCR. Furthermore, the relationships between their expression and clinicopathological features, as well as the survival prognosis of patients, were investigated.
    Results Compared with adjacent normal breast tissues, the expression of miR-27a-3p mRNA in breast tumor tissues was lower (P < 0.05), while that of YAP1 mRNA was higher (P < 0.05). A negative correlation was observed between the expression of miR-27a-3p mRNA and YAP1 mRNA in breast tumor tissues (r = −0.456, P < 0.05). The expression of miR-27a-3p mRNA was correlated with tumor diameter, histological grade, tumor staging by the TNM system, lymph node metastasis, and vascular invasion in patients with breast cancer (P < 0.05). The YAP1 mRNA expression was correlated with histological grade, tumor staging by the TNM system, lymph node metastasis, and vascular invasion (P < 0.05). Kaplan-Meier survival analysis revealed that the 3-year overall survival rate of the miR-27a-3p low-expression group was 71.60% (48/67), which was lower than the 91.50% (54/59) of the miR-27a-3p high-expression group (log-rank χ2 = 8.211, P = 0.004). The 3-year overall survival rate of the YAP1 high-expression group was 73.80% (45/61), lower than that of the YAP1 low-expression group (87.70%, 57/65) (log-rank χ2=4.429, P = 0.035). Multivariate regression analysis indicated that lymph node metastasis (hazard ratio HR = 1.409; 95% CI, 1.057-1.644; P = 0.046), vascular invasion (HR = 1.541; 95% CI, 1.076-1.869; P = 0.045), low miR-27a-3p mRNA expression (HR = 0.593; 95% CI, 0.388-0.925; P = 0.018), and high YAP1 mRNA expression (HR = 0.628; 95% CI, 0.405-0.912; P = 0.022) were relevant factors affecting the 3-year overall survival of patients with breast cancer.
    Conclusion A significant downregulation of miR-27a-3p mRNA and upregulation of YAP1 mRNA are observed in breast tumor tissues. The low expression of miR-27a-3p mRNA and the high expression of YAP1 mRNA are associated with adverse clinicopathological features and poor survival prognosis, and are risk factors affecting the 3-year overall survival of patients with breast cancer. They show promise as new potential therapeutic targets for breast cancer.

     

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