CTGF 和 Cyr61 在结直肠癌中的表达。

Expression of CTGF and Cyr61 in colorectal cancer.

机构信息

Department of Cancer Studies and Molecular Medicine, Infirmary Close, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, UK.

出版信息

J Clin Pathol. 2011 Jan;64(1):58-64. doi: 10.1136/jcp.2010.082768. Epub 2010 Nov 15.

DOI:10.1136/jcp.2010.082768

PMID:21081514

Abstract

BACKGROUND

The CCN genes encode secreted extracellular matrix proteins cysteine rich-61 (Cyr61), connective tissue growth factor (CTGF) and nephroblastoma overexpressed (Nov). They are involved in diverse cellular functions. Expression of these factors in tumours has produced conflicting results. More recently, research has focused on molecular biomarkers to indicate progression of a disease or the susceptibility of the disease to a given treatment.

AIMS

The purpose of this study was to determine the expression of CTGF and Cyr61 genes and proteins in colorectal cancer. Expression was compared with various clinicopathological parameters including Dukes' stage and TNM stage. We determined the in vitro effects of hypoxia on Cyr61 and CTGF expression in colorectal cancer cell lines.

RESULTS

Hypoxia significantly reduced CTGF mRNA expression (p<0.01) in HT29 and Caco-2 cell lines. Cyr61 was induced (p<0.01) in HT29 cell lines but significantly reduced (p<0.01) in Caco-2 cell lines under hypoxic conditions. High levels of CTGF and Cyr61 mRNA were found in colorectal cancer compared with normal colon (p<0.05). Expression was reduced in more advanced cancers (Dukes' C vs Dukes' A and B). There was a significant association between CTGF protein expression and advancing Dukes' stage (p<0.01), T stage (p<0.01) and lymph-node involvement (p<0.05), but there was no significant association between Cyr61 expression and clinicopathological parameters.

CONCLUSION

Upregulation of Cyr61 and CTGF gene expression in colorectal cancer suggests they have a role in tumour initiation or development. However, the genes are not as highly expressed in advanced stages of colorectal cancer, suggesting their role may be important at an early stage of tumour development. These genes maybe used as early biomarkers to risk-stratify patients. Hypoxia alters the expression of these genes in colorectal cancer cell lines. Further studies are needed to determine whether targeting these genes would be useful in future therapy.

摘要

背景

CCN 基因编码富含半胱氨酸的 61 型（Cyr61）、结缔组织生长因子（CTGF）和肾母细胞瘤过表达（Nov）等分泌型细胞外基质蛋白。它们参与多种细胞功能。这些因子在肿瘤中的表达产生了相互矛盾的结果。最近的研究集中在分子生物标志物上，以指示疾病的进展或疾病对特定治疗的敏感性。

目的

本研究旨在确定 CTGF 和 Cyr61 基因及其蛋白在结直肠癌中的表达。将表达与各种临床病理参数（包括 Dukes 分期和 TNM 分期）进行比较。我们还测定了缺氧对结直肠癌细胞系 Cyr61 和 CTGF 表达的体外影响。

结果

缺氧显著降低 HT29 和 Caco-2 细胞系 CTGF mRNA 的表达（p<0.01）。Cyr61 在 HT29 细胞系中被诱导（p<0.01），但在 Caco-2 细胞系中缺氧时显著降低（p<0.01）。与正常结肠相比，结直肠癌中 CTGF 和 Cyr61 mRNA 水平较高（p<0.05）。在更晚期的癌症中（Dukes' C 期比 Dukes' A 和 B 期），表达降低。CTGF 蛋白表达与 Dukes 分期进展（p<0.01）、T 分期（p<0.01）和淋巴结受累（p<0.05）显著相关，但 Cyr61 表达与临床病理参数无显著相关性。

结论

结直肠癌中 Cyr61 和 CTGF 基因表达的上调表明它们在肿瘤发生或发展中具有作用。然而，这些基因在结直肠癌的晚期阶段表达不高，表明它们的作用可能在肿瘤发展的早期阶段更为重要。这些基因可能被用作早期生物标志物来对患者进行风险分层。缺氧改变了结直肠癌细胞系中这些基因的表达。需要进一步研究以确定针对这些基因是否对未来的治疗有用。