Biotechnology Department, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran.
Urol J. 2020 Aug 31;18(2):186-193. doi: 10.22037/uj.v0i0.5664.
Muscle-invasive bladder cancer (MIBC) is associated with disease progression and metastasis leading to poor prognosis. Current chemotherapy approaches have not adequately increased patient survival. Therefore, in this study, tissue proteome of patients with MIBC was performed to introduce possible protein candidates for bladder cancer prognosis as well as targeted therapy.
After obtaining tumoral and non-tumoral tissues of MIBC patients, and normal bladder tissue of non-bladder cancer patients, two-dimensional gel electrophoresis (2-DE) and liquid chromatography-mass spectrometry (LC-MS/MS) were used to analyze tissue proteome. Gelsolin-like Actin-capping (CAPG) protein was further examined using Real-time PCR and western blot analysis.
The 2-DE analysis and LC-MS/MS identified CAPG protein as differentially expressed protein in tumor and non-tumor tissues of bladder cancer compared with normal tissues. Western blot analysis showed the CAPG overexpression in tumor tissues compared with normal tissues in a stage-dependent manner. Correspondingly, Real- time PCR showed a higher mRNA expression in tumoral bladder tissues than normal ones. CAPG mRNA overexpression had significantly a positive relation with tumor size (P = 0.019), the TNM staging (P = 0.001), and tumor differentiation (grade) (P = 0.006). Patients with lower levels of CAPG had higher recurrence-free survival in comparison with patients with higher levels (P = .027).
CAPG overexpression was correlated with size, stage, grade, and shorter time to recurrence of bladder cancer. Therefore, CAPG overexpression could be related to poor prognosis of bladder cancer. These results suggest that CAPG may be considered as a prognostic factor and also for targeted therapy in bladder cancer. Moreover, it could be concluded that cancerous and noncancerous tissues of MIBC have the same protein expression because 2-DE results showed the CAPG expression in cancer and adjacent cancer tissues of bladder while CAPG was not detectable in normal tissues of bladder.
肌层浸润性膀胱癌（MIBC）与疾病进展和转移相关，导致预后不良。目前的化疗方法未能充分提高患者的生存率。因此，在这项研究中，对 MIBC 患者的组织蛋白质组进行了分析，以寻找可能的膀胱癌预后和靶向治疗的蛋白候选物。
在获得 MIBC 患者的肿瘤和非肿瘤组织以及非膀胱癌患者的正常膀胱组织后，使用二维凝胶电泳（2-DE）和液相色谱-质谱联用（LC-MS/MS）分析组织蛋白质组。使用实时 PCR 和 Western blot 分析进一步研究了肌动蛋白帽蛋白（CAPG）。
2-DE 分析和 LC-MS/MS 鉴定出 CAPG 蛋白在肿瘤和非肿瘤组织中与正常组织相比存在差异表达。Western blot 分析显示，CAPG 在肿瘤组织中的表达水平高于正常组织，且具有分期依赖性。相应地，实时 PCR 显示肿瘤组织中的 CAPG mRNA 表达高于正常组织。CAPG mRNA 过表达与肿瘤大小（P = 0.019）、TNM 分期（P = 0.001）和肿瘤分化（分级）（P = 0.006）显著正相关。与 CAPG 水平较高的患者相比，CAPG 水平较低的患者无复发生存时间更长（P = 0.027）。
CAPG 的过表达与膀胱癌的大小、分期、分级和复发时间较短相关。因此，CAPG 的过表达可能与膀胱癌的不良预后有关。这些结果表明，CAPG 可能被视为膀胱癌的预后因素和靶向治疗的靶点。此外，可以得出结论，MIBC 的癌组织和非癌组织具有相同的蛋白表达，因为 2-DE 结果显示 CAPG 在膀胱癌的癌组织和相邻癌组织中表达，而在正常膀胱组织中无法检测到。
