da Silva-Camargo Claudia Caroline Veloso, Svoboda Baldin Rosimeri Kuhl, Costacurta Polli Nayanne Louise, Agostinho Amanda Pereira, Olandosk Marcia, de Noronha Lúcia, Sotomaior Vanessa Santos
Group for Advanced Molecular Investigation (NIMA), School of Health and Biosciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba 80215-901, Brazil.
Hospital de Clínicas da Universidade Federal do Paraná (HC-UFPR), Curitiba 80215-901, Brazil.
Cancer Biol Med. 2018 Feb;15(1):61-69. doi: 10.20892/j.issn.2095-3941.2017.0136.
Features of colorectal cancer such as natural history, molecular, chromosomal, and epigenetic alterations have been well described. However, there is still a lack of accurate prognostic markers, which is evident by the lower overall survival rates of patients with advanced cancer. Although alterations in parkin protein expression have been described in colorectal cancer, the functional significance of this protein remains unknown. The present study aimed to investigate the involvement of parkin expression in colorectal adenocarcinoma development and progression by evaluating the association between its expression, clinicopathological parameters, and expression of known proteins involved in colorectal cancer.
Tissue microarrays consisting of 73 tumor and 64 normal tissue samples were generated to examine parkin expression and localization by immunohistochemistry.
A positive correlation of parkin and APC expression was observed in the superficial, intermediate, and profound regions of all cases (ρ = 0.37; = 0.001). Parkin expression was also significantly associated with tumors in men ( = 0.049), those of the mucinous subtype ( = 0.028), and of advanced stage (III + IV, = 0.041). In addition, increased parkin expression was observed in the invasive front tumor region ( = 0.013). More importantly, a positive correlation was found between parkin expression and the overall survival of patients with advanced colorectal cancer ( = 0.019). Multivariate analysis showed that parkin expression was independent of any of the clinicopathological parameters evaluated in relation to patient survival.
These results suggest that parkin expression status can be used as a potential independent prognostic marker of survival in advanced colorectal cancer.
结直肠癌的特征，如自然史、分子、染色体和表观遗传改变等已得到充分描述。然而，仍缺乏准确的预后标志物，晚期癌症患者总体生存率较低就证明了这一点。尽管在结直肠癌中已描述了帕金蛋白表达的改变，但该蛋白的功能意义仍不清楚。本研究旨在通过评估帕金蛋白表达、临床病理参数以及结直肠癌相关已知蛋白表达之间的关联，来研究帕金蛋白表达在结直肠癌发生发展中的作用。
制作包含73个肿瘤组织和64个正常组织样本的组织芯片，通过免疫组织化学检测帕金蛋白的表达和定位。
在所有病例的浅表、中层和深层区域均观察到帕金蛋白与腺瘤性息肉病（APC）表达呈正相关（ρ = 0.37；P = 0.001）。帕金蛋白表达还与男性肿瘤（P = 0.049）、黏液亚型肿瘤（P = 0.028）以及晚期（III + IV期，P = 0.041）肿瘤显著相关。此外，在肿瘤浸润前沿区域观察到帕金蛋白表达增加（P = 0.013）。更重要的是，发现帕金蛋白表达与晚期结直肠癌患者的总生存期呈正相关（P = 0.019）。多变量分析表明，帕金蛋白表达与评估的任何与患者生存相关的临床病理参数无关。
这些结果表明，帕金蛋白表达状态可作为晚期结直肠癌生存的潜在独立预后标志物。
