甲状腺癌组织中微小RNA-495-3p、Holliday交叉识别蛋白表达水平及临床意义

刘培发; 侯文宇; 菅雁兵; 李佶阳

doi:10.7619/jcmp.20213538

甲状腺癌组织中微小RNA-495-3p、Holliday交叉识别蛋白表达水平及临床意义

Expression levels and clinical significance of microR-495-3p and Holliday junction recognition protein in thyroid cancer

摘要

摘要:
目的检测甲状腺癌组织中微小RNA-495-3p(miR-495-3p)、Holliday交叉识别蛋白(HJURP)的表达水平及临床意义。
方法选择行手术根治术切除并经病理检查确诊的甲状腺癌石蜡包埋标本67例及正常甲状腺组织石蜡包埋标本42例为研究对象，利用荧光定量聚合酶链反应(PCR)技术检测miR-495-3p水平，采用免疫组织化学法检测HJURP阳性表达情况，分析miR-495-3p、HJURP水平与甲状腺癌患者临床病理参数的关系。采用Kaplan-Meier生存曲线分析甲状腺癌组织中miR-495-3p、HJURP水平与患者预后的关系; 采用COX回归分析探讨影响甲状腺癌患者预后的不良因素。
结果 HJURP在癌组织中的阳性表达率为62.69%, 在正常甲状腺组织中的阳性表达率为26.19%, 差异有统计学意义(χ²=13.765, P < 0.01); miR-495-3p在甲状腺癌组织和正常甲状腺组织中的相对表达量分别为(0.76±0.21)、(1.26±0.40), 差异有统计学意义(t=8.539, P < 0.001); miR-495-3p、HJURP水平与甲状腺患者临床分期、淋巴结转移有关(P < 0.05); 临床分期Ⅲ~Ⅳ、发生淋巴结转移的甲状腺癌患者miR-495-3p的水平更低, HJURP蛋白阳性表达更高; miR-495-3p高表达患者3年累积生存率高于miR-495-3p低表达组，差异有统计学意义(χ²=8.478, P=0.004); HJURP阳性患者3年累积生存率为57.14%, 低于HJURP阴性患者的92.00%, 差异有统计学意义差异有统计学意义(χ²=9.093, P=0.003)。多因素分析结果显示，临床分期、淋巴结转移、miR-495-3p、HJURP是影响甲状腺癌患者预后不良的独立危险因素(P < 0.05)。
结论甲状腺癌组织中miR-495-3p表达下调, HJURP表达上调，与肿瘤临床分期、淋巴结转移及预后有关，可能参与了肿瘤细胞的分化、迁移等过程。

Abstract:
Objective To detect the expression levels of microRNA-495-3p (miR-495-3p) and Holliday junction recognition protein (HJURP) in thyroid cancer tissues and explore their clinical significance.
Methods A total of 67 paraffin-embedded specimens of thyroid cancer diagnosed by pathological examination and 42 paraffin-embedded specimens of normal thyroid tissue were selected as research objects. The miR-495-3p level was detected with fluorescence quantitative polymerase chain reaction (PCR) technology, the positive expression of HJURP was detected by immunohistochemistry, the relationships of miR-495-3p, HJURP levels with clinicopathological parameters in patients with thyroid cancer were analyzed. Kaplan-Meier survival curve was used to analyze the relationships of the levels of miR-495-3p and HJURP in thyroid cancer with the prognosis ofpatients; COX regression analysis was used to explore the adverse factors affecting the prognosis of thyroid cancer patients.
Results The positive expression rate of HJURP in cancer tissues was 62.69%, and was 26.19% in normal thyroid tissues (P < 0.01); the relative expression of miR-495-3p in thyroid cancer tissue and normal thyroid tissue was (0.76±0.21) and (1.26±0.40), respectively(t=8.539, P < 0.001); the levels of miR-495-3p and HJURP were related to the clinical stageand lymph node metastasis of thyroid patients (P < 0.05). The levels of miR-495-3p in patients with thyroid cancer in clinical stage of Ⅲ to Ⅳ and lymph nodemetastasis were lower, and their positive expression of HJURP protein were higher; the 3-year cumulative survival rates of patients with miR-495-3p high expression were significantly higher than in those with miR-495-3p low expression (χ²=8.478, P=0.004); the 3-year cumulative survival rate of patients with positive HJURP was significantly lower than that in those with negative HJURP (57.14% versus 92.00%, χ²=9.093, P=0.003); the results of multivariate analysis showed that clinical staging, lymph node metastasis, miR-495-3p, and HJURP were independent risk factors affecting the poor prognosis of patients with thyroid cancer (P < 0.05).
Conclusion In tissues of thyroid cancer, the expression of miR-495-3p is down-regulated, and the expression of HJURP is up-regulated, which are related to the clinical stage of the tumor, lymph node metastasis and prognosis, and may be involved in the differentiation and migration of tumor cells.

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