前列腺癌患者血浆miR-135、miR-103、miR-34b表达水平及其与临床病理特征和预后的关系

Expression of plasma miR-135,miR-103,miR-34b in prostate cancer and its relationship with clinicopathological features and prognosis

目的探究血浆微小RNA-135(miR-135)、miR-103、miR-34b在前列腺癌中的表达水平,分析三者与临床病理特征、临床预后的关系。方法前瞻性选取2018年5月至2021年6月临沂市肿瘤医院收治的前列腺癌患者87例(前列腺癌组)、良性前列腺增生患者83例(良性前列腺增生组)、体检健康者85名(健康对照组)为研究对象。采用实时荧光定量PCR测定3组研究对象的血浆miR-135、miR-103、miR-34b水平;比较前列腺癌患者治疗前后血浆miR-135、miR-103、miR-34b水平,分析血浆miR-135、miR-103、miR-34b表达与临床病理特征及预后的关系。结果前列腺癌组血浆miR-135水平明显高于良性前列腺增生组及健康对照组,miR-103、miR-34b水平明显低于良性前列腺增生组及健康对照组,差异均有统计学意义(P<0.05)。治疗后,前列腺癌患者血浆miR-135水平相比治疗前明显降低,miR-103、miR-34b水平相比治疗前明显升高,差异均有统计学意义(P<0.05)。前列腺癌患者血浆miR-135、miR-103、miR-34b表达与病理分级Gleason评分、TNM分期有关(P<0.05)。随访12~48个月,平均(27.63±4.89)个月;发生骨转移13例(14.94%,死亡3例),复发10例(11.49%,死亡4例);miR-135在有骨转移患者中表达高于无骨转移患者,在复发患者中表达高于无复发患者;miR-103、miR-34b在有骨转移患者中表达低于无骨转移患者,在复发患者中表达低于无复发患者,差异均有统计学意义(P<0.05)。miR-34b、miR-103降低是前列腺癌患者预后不良的危险因素(P<0.05),miR-135降低是前列腺癌患者预后不良的保护性因素(P<0.05)。受试者工作特征(ROC)曲线分析显示,3项联合预测前列腺癌预后的曲线下面积(AUC)为0.984,高于miR-135、miR-103、miR-34b单项检测(0.828、0.899、0.850)(Z=3.515、2.202、2.776,P=0.000、0.028、0.005)。结论前列腺癌患者血浆miR-135呈相对高表达,miR-103、miR-34b水平呈相对低表达;miR-135、miR-103、miR-34b与前列腺癌患者病理分级、TNM分期有关,可能参与肿瘤的病理生理过程;且3项联合检测对前列腺癌患者的预后具有较高预测价值。

Objective To investigate the expression levels of plasma microRNA-135(miR-135),miR-103,and miR-34b in prostate cancer,and analyze the relationship between the three and clinicopathological features and clinical prognosis.Methods A total of 87 patients(prostate cancer group),83 patients with benign prostatic hyperplasia(benign prostatic hyperplasia group),and 85 healthy patients(healthy control group)who underwent physical examination admitted to Linyi Cancer Hospital from May 2018 to June 2021 were selected as the research objects.The levels of miR-135,miR-103,and miR-34b in the plasma of the three groups were determined by real-time quantitative PCR;the levels of the three groups were compared before and after treatment in patients with prostate cancer,and the relationship between the three and clinicopathological characteristics and prognosis was analyzed.Results The levels of plasma miR-135 in prostate cancer group were higher than those in benign prostatic hyperplasia group and healthy control group,and the levels of miR-103 and miR-34b were lower than those in benign prostate hyperplasia group and healthy control group,and the differences were statistically significant(P<0.05).After treatment,the plasma levels of miR-135 in prostate cancer patients were lower than before treatment,and the levels of miR-103 and miR-34b were higher than before treatment,the differences were statistically significant(P<0.05).The expressions of miR-135,miR-103,and miR-34b in prostate cancer were related to pathological grade Gleason score and TNM stage(P<0.05).Follow-up was 12 to 48 months,with an average of(27.63±4.89)months;13 cases of bone metastases(14.94%,3 deaths),and 10 cases of recurrence(11.49%,4 deaths);miR-135 in patients with bone metastases The expression of miR-103 and miR-34b is higher in patients with bone metastasis than in patients without bone metastasis,and lower in patients with relapse than in patients without bone recurrence patients,the differences were statistically significant(P<0.05).Decreased miR-34b and miR-103 were risk factors for poor prognosis of prostate cancer patients(P<0.05),and decreased miR-135 was a protective factor for poor prognosis of prostate cancer patients(P<0.05).Receiver operator characteristic curve(ROC)curve analysis showed that the area under curve(AUC)of the three prognostic factors for the prognosis of prostate cancer was 0.984,which was higher than the single detection of miR-135,miR-103,and miR-34b(0.828,0.899,0.850)(Z=3.515,2.202,2.776,P=0.000,0.028,0.005).Conclusion Prostate cancer patients have relatively high expression of miR-135 and relatively low expression of miR-103 and miR-34b;miR-135,miR-103,miR-34b are related to pathological grade and TNM stage of prostate cancer patients,and may be involved in tumor Pathophysiological process;and the three combinations have a high predictive value for the prognosis of patients with prostate cancer.