The clinical perspectives of CDX2 expression in colorectal cancer: a qualitative systematic review

Abstract

Introduction: Homeobox genes are often deregulated in cancer. They can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. It is implicated in differentiation, proliferation, cell-adhesion, and migration. CDX2 has been proposed as a tumor suppressor in colorectal cancer but its role is still controversial. This systematic review were undertaken in order to clarify CDX2s role in colorectal cancer.

Methods: A literature search was performed in the MEDLINE database from 1966 to February 2014. Only studies in which all or a part of the experimental design were performed on human colorectal cancer tissue were included. Thus, studies solely performed in cell-lines or animal models were excluded.

Results: Fifty-two articles of relevance were identified. CDX2 expression was rarely lost in colorectal cancers, however the expression pattern may often be heterogeneous within the tumor and can be selectively down regulated at the invasive front and in tumor buddings. Loss of CDX2 expression is probably correlated to tumor grade, stage, right-sided tumor location, MMR-deficiency, CIMP, and BRAF mutations. The CDX2 gene is rarely mutated but the locus harboring the gene is often amplified and may suggest CDX2 as a linage-survival oncogene. CDX2 might be implicated in cell proliferation and migration through cross-talk with the Wnt-signaling pathway, tumor-stroma proteins, and inflammatory cytokines.

Conclusion: A clear role for CDX2 expression in colorectal cancer remains to be elucidated, and it might differ in relation to the underlying molecular pathways leading to the cancer formation.

Keywords: CDX2; Cancer biomarker; Colorectal cancer; Gastroenterology.