Zhou Kun, Liang Hongyan, Liu Yang, Yang Chun, Liu Peijia, Jiang Xiaofeng
Department of Clinical Biochemistry Laboratory, The 4th Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang, Harbin, People's Republic of China,
Tumour Biol. 2013 Dec;34(6):3691-9. doi: 10.1007/s13277-013-0952-3. Epub 2013 Jul 14.
Carboxypeptidase E (CPE) is one of the most important carboxypeptidases involved in biosynthesis of numerous peptide hormones and neurotransmitters and has an important role in endocrine regulation. A splice variant of CPE (CPE-ΔN) has been detected and the mechanism of CPE-ΔN action in tumorigenesis has been studied in many different cancers. The aim of this study was to examine CPE-ΔN expression in human colorectal cancer (CRC) and to evaluate its possible use as a potential prognostic marker. Two hundred nineteen primary colorectal tumors and corresponding normal tissues were included in the study. We have analyzed CPE-ΔN isoform expression by qRT-PCR and Western blot in 219 CRC patients. Correlations between CPE-ΔN mRNA expression and clinicopathological variables were determined with chi-square tests. Survival probabilities were determined using Kaplan-Meier analysis, and univariate and multivariate analyses of the prognostic factors were performed with a Cox regression model. Our results show that CPE-ΔN is overexpressed in colorectal tumor tissue and that high CPE-ΔN mRNA expression is closely correlated with tumor differentiation, pT classification, pN classification, tumor recurrence, and lymph node metastasis (P = 0.042, 0.036, 0.031, 0.006, and 0.008, respectively). However, no correlation was observed between CPE-ΔN expression and age, gender, tumor localization, gross features, and the tumor size. In addition, patients with high CPE-ΔN expression had a significantly shorter survival (P < 0.001, logrank test). Tumor differentiation, gross feature, pT classification, pN classification, tumor recurrence, lymph node metastasis, and CPE-ΔN status were significantly associated with poor prognosis after performing a univariate Cox survival analysis. High CPE-ΔN expression was also identified as an independent prognostic factor using a multivariate analysis (P = 0.011). Based on these results, we can conclude that CPE-ΔN expression might be a potential prognostic marker for colorectal cancer patients.
羧肽酶E（CPE）是参与多种肽类激素和神经递质生物合成的最重要的羧肽酶之一，在内分泌调节中起重要作用。已检测到CPE的一种剪接变体（CPE-ΔN），并且在许多不同癌症中研究了CPE-ΔN在肿瘤发生中的作用机制。本研究的目的是检测人结直肠癌（CRC）中CPE-ΔN的表达，并评估其作为潜在预后标志物的可能用途。该研究纳入了219例原发性结直肠肿瘤及相应的正常组织。我们通过qRT-PCR和蛋白质印迹分析了219例CRC患者中CPE-ΔN亚型的表达。采用卡方检验确定CPE-ΔN mRNA表达与临床病理变量之间的相关性。使用Kaplan-Meier分析确定生存概率，并采用Cox回归模型对预后因素进行单因素和多因素分析。我们的结果表明，CPE-ΔN在结直肠肿瘤组织中过表达，并且高CPE-ΔN mRNA表达与肿瘤分化、pT分类、pN分类、肿瘤复发和淋巴结转移密切相关（分别为P = 0.042、0.036、0.031、0.006和0.008）。然而，未观察到CPE-ΔN表达与年龄、性别、肿瘤定位、大体特征和肿瘤大小之间的相关性。此外，CPE-ΔN高表达的患者生存期明显较短（P < 0.001，对数秩检验）。进行单因素Cox生存分析后，肿瘤分化、大体特征、pT分类、pN分类、肿瘤复发、淋巴结转移和CPE-ΔN状态与预后不良显著相关。多因素分析也确定高CPE-ΔN表达是一个独立的预后因素（P = 0.011）。基于这些结果，我们可以得出结论，CPE-ΔN表达可能是结直肠癌患者的潜在预后标志物。
