Decreased expression of IGFBP6 correlates with poor survival in colorectal cancer patients

Background: The insulin-like growth factor binding protein 6 (IGFBP6), as a specific inhibitor of IGF-Ⅱ, is a candidate human anti-oncogene in multiple tumors. However, the expression of IGFBP6 in colorectal cancer (CRC) and prognostic significance are unclear.

Methods: In this study, we examined colorectal cancer tissues and adjacent normal tissues to determine the expression levels of IGFBP6 mRNA and protein by quantitative reverse-transcription polymerase chain reaction and tissue microarray immunohistochemistry analysis respectively. Moreover, we explored the effects of IGFBP6 on cell growth, migration and invasion by Cell Counting Kit-8(CCK8), colony formation and transwell migration assays. We also investigated whether IGFBP6 expression in tumor tissue correlated with various clinical parameters, including overall survival by univariate and multivariate analyses RESULTS: Both IGFBP6 mRNA and protein levels were significantly lower in colorectal cancer tissues than in adjacent normal colon. Downregulating IGFBP6 using RNAi increased CRC cell proliferation, migration and invasion. Low IGFBP6 expression correlated with poor overall survival in both univariate and multivariate analyses.

Conclusion: Our data suggest that IGFBP6 may act as a tumor suppressor gene in the development of CRC, and that low IGFBP6 expression could be used as an independent prognostic biomarker in CRC.