He Y J, Zhang D, Li L Y, Yang H X, Hu Z Z, Li X M
Department of Clinical Pathology, the People's Hospital of Baoan Shenzhen, the Second Affiliated Hospital of Shenzhen University, Shenzhen 518100,China.
Zhonghua Bing Li Xue Za Zhi. 2025 Jul 8;54(7):733-740. doi: 10.3760/cma.j.cn112151-20250108-00023.
To investigate the expression of SLIT2/ROBO1 in prostate cancer and its clinical significance. A total of 100 cases of radical prostatectomy paraffin specimens at Department of Clinical Pathology, the average age of the patients was (71.8±7.8) years, the People's Hospital of Baoan Shenzhen from January 2015 to December 2019 were collected and immunohistochemical staining was used to analyze the correlation between SLIT2/ROBO1 expression and clinicopathological features in prostate cancer.COX regression was used to analyze the influencing factors of biochemical recurrence in patients with prostate cancer after radical treatment.Prostate cancer cells PC3 and LNCaP were used as research objects, ROBO1 was silenced by small interfering RNA specific to human ROBO1, and its effect on the growth rate of prostate cancer was observed by CCK8 assay.Transwell cell migration and invasion assay was used to detect the effect of ROBO1 knock-down on the migration and invasion ability of prostate cancer cells.Protein immunoimprinting assay was used to detect the expression of TGF-β/SMAD pathway-related proteins after ROBO1 knockdown. The expressions of SLIT2 and ROBO1 in prostate cancer were increased with the increase of prostate cancer Gleason score system (Gleason score) and International Society of Urology Pathology score (ISUP)(<0.05). The expression was significantly up-regulated in prostate cancer tissues with lymph node metastasis (<0.01) and T3 stage.In addition, COX regression univariate analysis showed that age, preoperative PSA level, Gleason and ISUP scores, T stage, lymph node metastasis and ROBO1 protein expression status were correlated with postoperative biochemical recurrence.COX regression multivariate analysis showed that ROBO1 high expression, age, preoperative PSA value and T stagewere risk factors for the prognosis of prostate cancer (<0.05).The results of cell experiments showed that ROBO1 promoted the proliferation, migration and invasion of prostate cancer cells.The expression of TGF-β/SMAD was decreased after ROBO1 knockdown and SLIT2/ROBO1 inhibitor (P144)treatment, respectively. The high expression of SLIT2 and ROBO1 is associated with the progression and differentiation of prostate cancer.The high expression of ROBO1 is a risk factor for biochemical recurrence of prostate cancer.At the same time, ROBO1 can inhibit the migration and invasion of prostate cancer cells by regulating the TGF-β/SMAD signaling pathway.
探讨SLIT2/ROBO1在前列腺癌中的表达及其临床意义。收集2015年1月至2019年12月深圳市宝安区人民医院临床病理科100例前列腺癌根治术石蜡标本，患者平均年龄为（71.8±7.8）岁，采用免疫组织化学染色分析SLIT2/ROBO1表达与前列腺癌临床病理特征的相关性。采用COX回归分析前列腺癌根治术后患者生化复发的影响因素。以前列腺癌细胞PC3和LNCaP为研究对象，用针对人ROBO1的小干扰RNA沉默ROBO1，通过CCK8法观察其对前列腺癌细胞生长速度的影响。采用Transwell细胞迁移和侵袭实验检测ROBO1敲低对前列腺癌细胞迁移和侵袭能力的影响。采用蛋白质免疫印迹法检测ROBO1敲低后TGF-β/SMAD通路相关蛋白的表达。前列腺癌中SLIT2和ROBO1的表达随前列腺癌Gleason评分系统（Gleason评分）和国际泌尿病理学会评分（ISUP）的升高而增加（P<0.05）。在有淋巴结转移的前列腺癌组织（P<0.01）和T3期，表达显著上调。此外，COX回归单因素分析显示，年龄、术前PSA水平、Gleason和ISUP评分、T分期、淋巴结转移和ROBO1蛋白表达状态与术后生化复发相关。COX回归多因素分析显示，ROBO1高表达、年龄、术前PSA值和T分期是前列腺癌预后的危险因素（P<0.05）。细胞实验结果显示，ROBO1促进前列腺癌细胞的增殖、迁移和侵袭。ROBO1敲低和SLIT2/ROBO1抑制剂（P144）处理后，TGF-β/SMAD的表达分别降低。SLIT2和ROBO1的高表达与前列腺癌的进展和分化相关。ROBO高表达是前列腺癌生化复发的危险因素。同时，ROBO1可通过调节TGF-β/SMAD信号通路抑制前列腺癌细胞的迁移和侵袭。
