miR-296-5p、Skp2、RPL6与前列腺癌病理特征的关系及对手术预后的影响

Association of miR-296-5p，S-phase kinase-associated protein 2， and ribosomal protein L6 with the pathological features of prostate cancer and their influence on surgical prognosis

摘要

目的 探讨微小RNA-296-5p、S期激酶相关蛋白2（S-phase kinase-associated protein 2，Skp2）、核糖体蛋白L6（ribosomal protein L6，RPL6）与前列腺癌病理特征的关系及对手术预后的影响。 方法 选取2018年1月至2023年1月120例前列腺患者，均行腹腔镜前列腺癌术治疗，对比不同病理特征患者miR-296-5p、Skp2、RPL6 mRNA表达水平，分析各指标与病理特征的关系。根据术后1年是否生化复发分为复发组（n=21）与未复发组（n=97），比较2组临床资料、miR-296-5p、Skp2、RPL6 mRNA表达水平，分析miR-296-5p、Skp2、RPL6对手术预后的影响及预测价值。 结果 不同病理分期、Gleason评分、术前血清前列腺特异性抗原（prostate specific antigen，PSA）水平、淋巴结转移患者miR-296-5p、Skp2、RPL6 mRNA表达水平比较，差异有统计学意义（F=12.927、22.416、10.088、34.239、20.180、12.208，t=4.649、-5.770、-5.713、4.716、-5.647、-6.884，均P=0.000）；miR-296-5p与Gleason评分、病理分期、术前血清前列腺特异性抗原（prostate specific antigen，PSA）水平、淋巴结转移呈负相关（r=-0.578、-0.539、-0.517、-0.556，均P<0.001），Skp2、RPL6 mRNA与Gleason评分、病理分期、术前血清PSA水平、淋巴结转移呈正相关（r=0.531、0.507、0.476、0.493、0.494、0.473、0.420、0.505，均P<0.001）；复发组淋巴结转移、病理分期、切缘阳性率、Gleason评分、高于未复发组，术后辅助治疗率低于未复发组（P<0.05）；复发组miR-296-5p表达水平低于未复发组，Skp2、RPL6 mRNA表达水平高于未复发组（P<0.05）；校正前，logistic回归分析，病理分期、Gleason评分、淋巴结转移、切缘阳性、术后辅助治疗、miR-296-5p、Skp2、RPL6 mRNA是前列腺癌患者术后生化复发的影响因素（P<0.05），校正后，miR-296-5p、Skp2、RPL6 mRNA仍是前列腺癌患者术后生化复发的影响因素（P<0.05）；miR-296-5p、Skp2、RPL6联合预测前列腺术后生化复发的AUC为0.902（95%CI=0.833～0.949），大于各指标单独预测（P<0.05）。 结论 前列腺癌患者miR-296-5p、Skp2、RPL6表达水平与病理特征、术后复发密切相关，三者联合预测前列腺术后生化复发具有较高的参考价值。

Abstract

Objective To explore the relationship between microRNA-296-5p（miR-296-5p），S-phase kinase-associated protein 2（Skp2），ribosomal protein L6 （RPL6） and pathological characteristics of prostate cancer，as well as their impact on surgical prognosis. Methods A total of 120 patients with prostate cancer who were treated from January 2018 to January 2023 were enrolled，and all patients underwent laparoscopic therapy for prostate cancer. The mRNA expression levels of miR-296-5p，Skp2，and RPL6 were compared between the patients with different pathological features，and the association between each indicator and pathological features was analyzed. According to the presence or absence of recurrence at 1 year after surgery，the patients were divided into recurrence group with 21 patients and non-recurrence group with 97 patients. The two groups were compared in terms of clinical data and the mRNA expression levels of miR-296-5p，Skp2，and RPL6，and the influence of miR-296-5p，Skp2，and RPL6 on surgical prognosis and their predictive value were analyzed. Results There were statistically significant differences in the expression levels of miR-296-5p，Skp2，and RPL6 mRNA among patients with different pathological stages，Gleason scores，preoperative serum prostate specific antigen（PSA） levels，and lymph node metastasis（F=12.927，22.416，10.088，34.239，20.180，12.208；t=4.649，-5.770，-5.713，4.716，-5.647，-6.884；P=0.000 for all）. miR-296-5p was negatively correlated with Gleason score，pathological stage，preoperative serum PSA level，and lymph node metastasis（r=-0.578，-0.539，-0.517，-0.556；P<0.001 for all），while Skp2 and RPL6 mRNA were positively correlated with Gleason score，pathological stage，preoperative serum PSA level，and lymph node metastasis（r=0.531，0.507，0.476，0.493，0.494，0.473，0.420，0.505；P<0.001 for all）. Compared with the non-recurrence group，the recurrence group had significantly higher lymph node metastasis，pathological stage，rate of positive margin，and Gleason score and a significantly lower rate of postoperative adjuvant therapy（P<0.05）. Compared with the non-recurrence group，the recurrence group had a significantly higher expression level of miR-296-5p and significantly lower mRNA expression levels of Skp2 and RPL6（P<0.05）. Before correction，the logistic regression analysis showed that pathological stage，Gleason score，lymph node metastasis，positive surgical margin，postoperative adjuvant therapy，and the mRNA expression levels of miR-296-5p，Skp2，and RPL6 mRNA were influencing factors for postoperative biochemical recurrence in patients with prostate cancer（P<0.05），and after correction，the mRNA expression levels of miR-296-5p，Skp2，and RPL6 were still influencing factors for postoperative biochemical recurrence in patients with prostate cancer （P<0.05）. The ROC curve analysis showed that the combination of miR-296-5p，Skp2，and RPL6 had an area under the ROC curve of 0.902（95%CI=0.833～0.949） in predicting biochemical recurrence after prostate cancer surgery，with a significantly larger AUC than each indicator alone（P<0.05）. Conclusion The expression levels of miR-296-5p，Skp2，and RPL6 are closely associated with pathological features and postoperative recurrence in patients with prostate cancer，and the combination of the three indicators has a high reference value in predicting biochemical recurrence after prostate cancer surgery.

关键词

微小RNA-296-5p / S期激酶相关蛋白2 / 核糖体蛋白L6 / 前列腺癌 / 病理特征 / 手术 / 预后

Key words

microRNA-296-5p / S-phase kinase-associated protein 2 / ribosomal protein L6 / prostate cancer / pathological features / surgery / prognosis

基金资助

2023年度河南省医学科技攻关计划资助项目(LHGJ20230885)