Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, PR China.
PLoS One. 2013 Jun 17;8(6):e66524. doi: 10.1371/journal.pone.0066524. Print 2013.
Retinoblastoma binding protein 6 (RBBP6) plays an important role in chaperone-mediated ubiquitination and interacts with TP53 in carcinogenesis. However, the clinicopathologic significance of RBBP6 expression in colon cancer is unknown; in particular, the prognostic value of RBBP6 combined with TP53 expression has not been explored. Therefore, quantitative real-time PCR and western blot analyses were performed to detect RBBP6 expression in colon cancer tissues. RBBP6 and TP53 expression were assessed by immunohistochemistry in a tissue microarray format, in which the primary colon cancer tissue was paired with noncancerous tissue. Tissue specimens were obtained from 203 patients. We found that RBBP6 was overexpressed in colon tumorous tissues and was significantly associated with clinical stage, depth of tumor invasion, lymph node metastasis (LNM), distant metastasis, and histologic grade. Further studies revealed that a corresponding correlation between RBBP6 overexpression and mutant TP53 was evident in colon cancer (r = 0.450; P<0.001). RBBP6 expression was an independent prognostic factor for overall survival (OS) and disease free survival (DFS). Interestingly, patients with tumors that had both RBBP6 overexpression and mutant TP53 protein accumulation relapsed and died within a significantly short period after surgery (P<0.001). Multivariate analysis showed that patients with LNM and patients with both RBBP6- and TP53-positive tumors had extremely poor OS (HR 6.75; 95% CI 2.63-17.35; P<0.001) and DFS (HR 8.08; 95% CI 2.80-23.30; P<0.001). These clinical findings indicate that the assessment of both RBBP6 and mutant TP53 expression will be helpful in predicting colon cancer prognosis.
视网膜母细胞瘤结合蛋白 6（RBBP6）在伴侣介导的泛素化中发挥重要作用，并在致癌作用中与 TP53 相互作用。然而，RBBP6 在结肠癌中的表达的临床病理意义尚不清楚；特别是，RBBP6 与 TP53 表达的预后价值尚未被探索。因此，进行了定量实时 PCR 和 Western blot 分析以检测结肠癌组织中的 RBBP6 表达。采用组织微阵列格式通过免疫组织化学评估 RBBP6 和 TP53 的表达，其中原发性结肠癌组织与非癌组织配对。从 203 例患者中获得组织标本。我们发现 RBBP6 在结肠癌肿瘤组织中过表达，并且与临床分期、肿瘤侵袭深度、淋巴结转移（LNM）、远处转移和组织学分级显著相关。进一步的研究表明，在结肠癌中，RBBP6 过表达与突变型 TP53 之间存在相应的相关性（r=0.450；P<0.001）。RBBP6 表达是总生存期（OS）和无病生存期（DFS）的独立预后因素。有趣的是，具有 RBBP6 过表达和突变型 TP53 蛋白积累的肿瘤患者在手术后的短时间内复发和死亡（P<0.001）。多变量分析显示，有 LNM 患者和 RBBP6 和 TP53 阳性肿瘤患者的 OS（HR 6.75；95%CI 2.63-17.35；P<0.001）和 DFS（HR 8.08；95%CI 2.80-23.30；P<0.001）极差。这些临床发现表明，评估 RBBP6 和突变型 TP53 的表达将有助于预测结肠癌的预后。
