Department of Gastrointestinal and Pediatric Surgery, Mie Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Med Oncol. 2013;30(3):620. doi: 10.1007/s12032-013-0620-x. Epub 2013 Jun 8.
Dual-specificity protein phosphatase 4 (DUSP4), a negative regulator of extracellular-regulated kinase activity, is a potential mediator of resistance to chemotherapy and a tumor suppressor. The aim of this study is to clarify the association between DUSP4 gene expression and clinical outcome in patients with colorectal cancer. Patients who underwent surgery for colorectal cancer were enrolled in this study (n = 212). We investigated DUSP4 gene expression by real-time reverse transcription polymerase chain reaction in colorectal cancer tissue and paired normal mucosa. Immunohistochemical analyses of DUSP4 and ERK1/2 were also conducted. Additionally, we examined the relationship between gene expression and KRAS mutation in 74 of the 212 patients. DUSP4 expression in tumor tissues was significantly higher than that in matched normal mucosa (P < 0.0001). Decreased DUSP4 expression was significantly associated with advanced T classification, lymphatic invasion, vascular invasion, advanced stage, and liver and lung metastases. Logistic regression analysis revealed that decreased DUSP4 expression was an independent risk factor for synchronous distant metastases (P = 0.006). Increased DUSP4 expression was significantly associated with better prognosis (P = 0.0162). Immunohistochemical examination showed DUSP4 expression in the nucleus and cytoplasm of cancer cells, and no correlation was observed between DUSP4 and ERK1/2 expression. There was no significant correlation between DUSP4 expression and KRAS mutation. In conclusion, DUSP4 expression in colorectal cancer was negatively correlated with factors reflecting tumor progression, including distant metastases. Our data suggest that DUSP4 may act as a tumor suppressor in colorectal cancer.
双重特异性蛋白磷酸酶 4（DUSP4）是细胞外调节激酶活性的负调节剂，是化疗耐药和肿瘤抑制的潜在介质。本研究旨在阐明 DUSP4 基因表达与结直肠癌患者临床结局的关系。本研究纳入了接受结直肠癌手术的患者（n=212）。我们通过实时逆转录聚合酶链反应（PCR）检测结直肠癌组织和配对正常黏膜中的 DUSP4 基因表达。还进行了 DUSP4 和 ERK1/2 的免疫组织化学分析。此外，我们在 212 例患者中的 74 例中检查了基因表达与 KRAS 突变之间的关系。肿瘤组织中的 DUSP4 表达明显高于配对的正常黏膜（P<0.0001）。DUSP4 表达降低与 T 分期较晚、淋巴血管侵犯、晚期、肝肺转移显著相关。Logistic 回归分析显示，DUSP4 表达降低是同步远处转移的独立危险因素（P=0.006）。DUSP4 表达增加与较好的预后显著相关（P=0.0162）。免疫组织化学检查显示癌细胞的核和细胞质中存在 DUSP4 表达，但 DUSP4 与 ERK1/2 表达之间无相关性。DUSP4 表达与 KRAS 突变无显著相关性。总之，结直肠癌中 DUSP4 的表达与反映肿瘤进展的因素呈负相关，包括远处转移。我们的数据表明 DUSP4 可能在结直肠癌中作为肿瘤抑制因子发挥作用。
