Kim Sang Hoon, Kim Tae-Jung, Shin Dongho, Hur Kyung Jae, Hong Sung-Hoo, Lee Ji Youl, Ha U-Syn
Department of Urology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Gland Surg. 2021 Oct;10(10):2956-2965. doi: 10.21037/gs-21-406.
The purpose of this study is to investigate the correlation between ROBO1 expression and prostate cancer aggressiveness.
ROBO1 expression was evaluated in normal prostate epithelial cells (PrEC) and different prostate cancer cell lines by Western blot analysis. The migration and invasion of native and ROBO1 knockdown cells were evaluated using migration chambers and a Matrigel-coated membrane, respectively. Samples from 145 patients who underwent radical prostatectomy between June 2000 and June 2008, were retrieved from the paraffin files for tissue microarray (TMA) with immunohistochemical analysis. Biochemical recurrence (BCR)-free survival curves were estimated using the Kaplan-Meier and Cox regression methods in two groups of patients classified according to the degree of ROBO1 expression (low or high expression).
ROBO1 is highly expressed in the prostate cancer cell lines. All ROBO1 knockdown cells (PC3, 22Rv1 and DU 145) showed markedly decreased migration and invasiveness compared to native cells. In 145 patients with radical prostatectomy, the Kaplan-Meier curves and log-rank test for BCR-free survival stratified by ROBO1 expression in organ-confined (pT2) or not (pT3), showed significant differences in 10-year survival between the ROBO1 high and low expression groups (87.2% versus 52.6% in pT2; P=0.047, 51.0% versus 36.9% in pT3; P=0.033). The multivariable-adjusted model showed a markedly increased hazard ratio (HR) in patients with high ROBO1 expression compared to the patients with low ROBO1expression in every model.
ROBO1 may play an important role in the migration and invasion of prostate cancer cells, and was independently associated with BCR.
本研究旨在探讨ROBO1表达与前列腺癌侵袭性之间的相关性。
通过蛋白质免疫印迹分析评估正常前列腺上皮细胞（PrEC）和不同前列腺癌细胞系中ROBO1的表达。分别使用迁移小室和基质胶包被的膜评估天然细胞和ROBO1基因敲低细胞的迁移和侵袭能力。从2000年6月至2008年6月期间接受根治性前列腺切除术的145例患者的石蜡切片中获取样本，用于制作组织芯片（TMA）并进行免疫组化分析。根据ROBO1表达程度（低表达或高表达）将患者分为两组，采用Kaplan-Meier法和Cox回归法估计无生化复发（BCR）生存曲线。
ROBO1在前列腺癌细胞系中高表达。与天然细胞相比，所有ROBO1基因敲低细胞（PC3、22Rv1和DU 145）的迁移和侵袭能力均显著降低。在145例接受根治性前列腺切除术的患者中，根据ROBO1表达情况对器官局限性（pT2）或非器官局限性（pT3）患者的无BCR生存进行Kaplan-Meier曲线分析和对数秩检验，结果显示ROBO1高表达组和低表达组在10年生存率上存在显著差异（pT2中分别为87.2%和52.6%；P=0.047，pT3中分别为51.0%和36.9%；P=0.033）。多变量调整模型显示，与ROBO1低表达患者相比，ROBO1高表达患者在每个模型中的风险比（HR）均显著增加。
ROBO1可能在前列腺癌细胞的迁移和侵袭中起重要作用，并且与BCR独立相关。
