三阴性乳腺癌组织长链非编码RNA-P21、microRNA-17-3p的表达及其临床意义

Expression and clinical significance of LncRNA-P21 and microRNA-17-3p in triple negative breast cancer tissues

摘要:

目的 探讨三阴性乳腺癌组织中长链非编码RNA-P21（LncRNA-P21）、microRNA-17-3p（miR-17-3p）的表达，分析其与三阴性乳腺癌患者的临床病理特征及预后的关系。方法 选取2016年1月—2017年5月南通大学附属医院收治的106例三阴性乳腺癌患者经手术切除的癌组织和癌旁组织（距离癌组织至少5 cm）标本，采用实时荧光定量聚合酶链反应检测癌组织、癌旁组织中LncRNA-P21和miR-17-3p的表达；收集患者的临床病理特征资料，分析LncRNA-P21、miR-17-3p表达与临床病理特征的关系；术后随访5年，采用Kaplan-Meier法绘制不同LncRNA-P21、miR-17-3p表达三阴性乳腺癌患者的生存曲线；Cox回归分析影响三阴性乳腺癌患者预后的因素。结果 癌组织LncRNA-P21 mRNA相对表达量低于癌旁组织（P <0.05）；癌组织miR-17-3p mRNA相对表达量高于癌旁组织（P <0.05）。临床Ⅲ期、腋窝淋巴结转移、Ki-67≥ 30%三阴性乳腺癌组织中LncRNA-P21 mRNA相对表达量低于临床Ⅰ、Ⅱ期，无腋窝淋巴结转移和Ki-67< 30%（P <0.05）；临床Ⅲ期、腋窝淋巴结转移、Ki-67≥ 30%三阴乳腺癌组织中miR-17-3p mRNA相对表达量高于临床Ⅰ、Ⅱ期，无腋窝淋巴结转移和Ki-67阴性表达（P <0.05）。不同年龄、肿瘤直径、分化程度、绝经状态的三阴性乳腺癌患者LncRNA-P21、miR-17-3p mRNA相对表达量比较，差异无统计学意义（P >0.05）。三阴性乳腺癌组织中LncRNA-P21表达与miR-17-3p表达呈负相关（r =-0.570，P <0.05）。LncRNA-P21低表达组5年无病生存期（DFS）和总生存期（OS）生存率低于LncRNA-P21高表达组（P <0.05），miR-17-3p高表达组5年DFS、OS生存率低于miR-17-3p低表达组（P <0.05）。单因素Cox回归分析结果显示，分化程度、TNM分期、腋窝淋巴结转移、LncRNA-P21、miR-17-3p是三阴性乳腺癌患者预后的影响因素（P <0.05）；多因素Cox风险比例回归分析结果显示，腋窝淋巴结转移、miR-17-3p是三阴性乳腺癌患者预后不良的危险因素（P <0.05），LncRNA-P21是保护因素（P <0.05）。结论 三阴性乳腺癌组织LncRNA-P21表达下调，miR-17-3p表达上调，且与乳腺癌Ki-67≥ 30%、临床Ⅲ期、腋窝淋巴结转移及预后不良有关。

Abstract:

Objective To investigate the relationship of LncRNA-P21, microRNA-17-3p (miR-17-3p) expression with clinicopathological features and prognosis in triple-negative breast cancer.Methods From January 2016 to May 2017, 106 patients with triple-negative breast cancer who underwent surgical resection of cancer tissues and adjacent tissues (at least 5 cm away from cancer tissues) were selected. Real-time quantitative polymerase chain reaction was used to detect the expression of LncRNA-P21 and miR-17-3p in tissue samples. Clinicopathological data of patients were collected, and the relationship between LncRNA-P21, miR-17-3p expression and clinicopathological features of patients was analyzed. After 5 years of follow-up, Kaplan-Meier method was used to draw the survival curves of triple-negative breast cancer under different expressions of LncRNA-P21 and miR-17-3p. Cox regression analysis was used to analyze the factors affecting the prognosis of triple negative breast cancer patients.Results The expression of LncRNA-P21 in cancer tissue was lower than that in adjacent tissues (P < 0.05); The expression of miR-17-3p in cancer tissue was higher than that in adjacent tissues (P < 0.05). The expression of LncRNA-P21 in triple-negative breast cancer tissue with TNM Ⅲ, axillary lymph node metastasis, and Ki-67 ≥ 30% was lower than that in TNM Ⅰ-Ⅱ, no axillary lymph node metastasis, and Ki-67 < 30% (P < 0.05), and the expression of miR-17-3p was higher than that in TNM Ⅰ-Ⅱ, no axillary lymph node metastasis, and Ki-67 negative (P < 0.05). There was no significant difference in the expression of LncRNA-P21 and miR-17-3p in different age, tumor diameter, degree of differentiation, and menopausal status (P > 0.05). The expression of LncRNA-P21 was negatively correlated with the expression of miR-17-3p in triple negative breast cancer (r = -0.570, P < 0.05). The disease-free survival (DFS) and total survival (OS) survival rates in the low expression group of LncRNA-P21 were lower than those in the high expression group of LncRNA-P21 (P < 0.05). The survival rate of DFS and OS in the high expression group of miR-17-3p was lower than that in the low expression group of miR-17-3p (P < 0.05). Univariable Cox regression analysis results showed that differentiation degree, TNM stage, axillary lymph node metastasis, LncRNA-P21, and miR-17-3p were the prognostic factors of triple negative breast cancer patients (P < 0.05). Multi-factor Cox regression analysis results showed that axillary lymph node metastasis and miR-17-3p were risk factors for poor prognosis of triple negative breast cancer patients (P < 0.05), and LncRNA-P21 was a protective factor (P < 0.05).Conclusion The expression of LncRNA-P21 is down-regulated and miR-17-3p is up-regulated in triple negative breast cancer tissues, which is related to the positive expression of Ki-67, TNM stage Ⅲ, axillary lymph node metastasis, and poor prognosis of breast cancer.