Zhao Xiao-Dong, Tang Zi-Lu, Wang Zu-Heng, Dong Jie, Xu Song
Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210002, China.
Department of Urology, General Hospital of Eastern Theater Command / Jinling Hospital Affiliated to Nanjing University School of Medicine, Nanjing, Jiangsu 210002, China.
Zhonghua Nan Ke Xue. 2022 Nov;28(11):996-1005.
To explore the value of miR-129 in the diagnosis, treatment and prediction of the clinical prognosis of PCa by observing the correlation between miR-129 and the progression of the malignancy.
This retrospective analysis included 310 male patients who visited the Department of Urology of the General Hospital of Eastern Theater Command from January 2014 to January 2022, 80 as normal healthy men, 80 with BPH, and the other 150 with PCa treated by radical prostatectomy without chemotherapy, radiotherapy or androgen-deprivation therapy. We determined the miR-129 expression in the serum and prostatic tissue of all the subjects by real-time quantitative PCR (RT-qPCR), performed pathological grading of the primary cancerous and pericancerous (≥ 3 cm from the focus) prostate tissues from the 150 PCa patients, collected the demographic and clinical data on all the subjects, and analyzed the correlation of their demographic data with the clinical parameters. We selected and transfected PC-3 and DU-145 cell lines with miR-129 precursor or miR-129 scramble, assessed the proliferation ability of each cell line and detected the expression levels of related proteins by cell proliferation assay and Western blot.
The expression of miR-129 was significantly decreased in the serum of the PCa patients compared with that in the normal healthy men and BPH patients (P < 0.01), so was it in the PCa tissue in comparison with that in the pericancerous prostatic tissue (P < 0.01), and it was negatively correlated with the preoperative serum PSA level (P < 0.001), histological grade (P < 0.001), pathological stage (P < 0.001), Gleason score (P < 0.001), lymph node metastasis (P = 0.02), angiolymphatic invasion (P = 0.021) and biochemical recurrence (BCR) (P=0.001). Kaplan-Meier analysis showed a strong correlation of down-regulated miR-129 expression with a lower BCR-free survival rate, while multivariate survival analysis indicated that the expression of miR-129 was an independent prognostic indicator of BCR-free survival of the PCa patients (P < 0.001). Highly expressed miR-129 significantly inhibited the proliferation of PCa cells by regulating the expressions of cell cycle-regulatory proteins.
The expression of miR-129 is significantly down-regulated in PCa tissues, which plays an important role in inhibiting the proliferation of PCa cells and tumor progression and improving BCR-free survival. Therefore, miR-129 can be considered as a new independent biomarker for the diagnosis, treatment and prediction of the clinical prognosis of PCa.
通过观察miR - 129与恶性肿瘤进展之间的相关性，探讨其在前列腺癌（PCa）临床诊断、治疗及预后预测中的价值。
本回顾性分析纳入了2014年1月至2022年1月在东部战区总医院泌尿外科就诊的310例男性患者，其中80例为正常健康男性，80例为良性前列腺增生（BPH）患者，另外150例为接受了前列腺癌根治术且未进行化疗、放疗或雄激素剥夺治疗的PCa患者。我们通过实时定量聚合酶链反应（RT - qPCR）测定了所有受试者血清和前列腺组织中的miR - 129表达，对150例PCa患者的原发性癌组织及癌旁（距病灶≥3 cm）前列腺组织进行了病理分级，收集了所有受试者的人口统计学和临床数据，并分析了其人口统计学数据与临床参数之间的相关性。我们选用miR - 129前体或miR - 129乱序序列转染PC - 3和DU - 145细胞系，通过细胞增殖试验和蛋白质免疫印迹法评估各细胞系的增殖能力并检测相关蛋白的表达水平。
与正常健康男性和BPH患者相比，PCa患者血清中miR - 129的表达显著降低（P < 0.01），与癌旁前列腺组织相比，PCa组织中的miR - 129表达也显著降低（P < 0.01），且其与术前血清前列腺特异抗原（PSA）水平（P < 0.001）、组织学分级（P < 0.001）、病理分期（P < 0.001）、Gleason评分（P < 0.001）、淋巴结转移（P = 0.02）、血管淋巴管浸润（P = 0.021）及生化复发（BCR）（P = 0.001）呈负相关。Kaplan - Meier分析显示，miR - 129表达下调与较低的无BCR生存率密切相关，而多因素生存分析表明，miR - 129的表达是PCa患者无BCR生存的独立预后指标（P < 故结论：PCa组织中miR - 129的表达显著下调，其在抑制PCa细胞增殖、肿瘤进展及提高无BCR生存率方面发挥着重要作用。因此，miR - 129可被视为PCa临床诊断、治疗及预后预测的一种新的独立生物标志物。 001）。高表达的miR - 129通过调节细胞周期调节蛋白的表达显著抑制了PCa细胞的增殖。
