Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
J Transl Med. 2013 Jun 20;11:151. doi: 10.1186/1479-5876-11-151.
Colorectal cancer (CRC) remains one of the most common cancers worldwide. We observed that MUC20 was significantly up-regulated in CRC patients with poor prognosis based on the microarray analysis. However, little is known about the role of MUC20 in CRC.
Microarray experiments were performed on the Affymetrix U133 plus 2.0 GeneChip Array. The protein and mRNA levels of MUC20 were examined by immunohistochemistry (IHC) and Real-Time quantitative PCR (RT-qPCR) in CRC tissues and adjacent noncancerous tissues (ANCT). ShRNA and overexpression plasmids were used to regulate MUC20 expression in CRC cell lines in vitro; wound healing, Transwell migration assays, and Western blotting were used to detect migration and invasion changes.
MUC20 was one of the up-regulated genes in CRC patients with poor prognosis by microarray. Using IHC and RT-qPCR, we showed that MUC20 expression was significantly higher in CRC tissues than in ANCT (P < 0.05). We further showed that MUC20 overexpression was correlated with recurrence and poor outcome (P < 0.05). The Kaplan-Meier survival curves indicated that disease-free survival (DFS) and overall survival (OS) were significantly worse in CRC patients with MUC20 overexpression. The Cox multivariate analysis revealed that MUC20 overexpression and TNM stage were independent prognostic factors. Elevated expression of MUC20 in cells promoted migration and invasion, whereas ShRNA-mediated knockdown inhibited these processes. In addition, Western blotting demonstrated that MUC20-induced invasion was associated with MMP-2, MMP-3, and E-cadherin.
Cumulatively, MUC20 may serve as an important predictor of recurrence and poor outcome for CRC patients. MUC20 overexpression could enhance migration and invasion abilities of CRC cells. Translation of its roles into clinical practice will need further investigation and additional test validation.
结直肠癌（CRC）仍然是全球最常见的癌症之一。我们通过微阵列分析发现，MUC20 在预后不良的 CRC 患者中显著上调。然而，关于 MUC20 在 CRC 中的作用知之甚少。
使用 Affymetrix U133 plus 2.0 GeneChip 阵列进行微阵列实验。通过免疫组织化学（IHC）和实时定量 PCR（RT-qPCR）检测 CRC 组织和相邻非癌组织（ANCT）中的 MUC20 蛋白和 mRNA 水平。体外使用 shRNA 和过表达质粒调节 CRC 细胞系中的 MUC20 表达；使用划痕愈合、Transwell 迁移实验和 Western blot 检测迁移和侵袭变化。
MUC20 是微阵列中预后不良的 CRC 患者上调的基因之一。通过 IHC 和 RT-qPCR，我们发现 MUC20 在 CRC 组织中的表达明显高于 ANCT（P<0.05）。我们进一步表明，MUC20 的过表达与复发和不良预后相关（P<0.05）。Kaplan-Meier 生存曲线表明，MUC20 过表达的 CRC 患者无病生存期（DFS）和总生存期（OS）明显较差。Cox 多因素分析显示，MUC20 过表达和 TNM 分期是独立的预后因素。细胞中 MUC20 的高表达促进迁移和侵袭，而 shRNA 介导的敲低抑制这些过程。此外，Western blot 表明，MUC20 诱导的侵袭与 MMP-2、MMP-3 和 E-钙黏蛋白有关。
综上所述，MUC20 可能是 CRC 患者复发和不良预后的重要预测因子。MUC20 的过表达可以增强 CRC 细胞的迁移和侵袭能力。将其作用转化为临床实践还需要进一步的研究和额外的测试验证。
