Integrated analysis of genes associated with poor prognosis of patients with colorectal cancer liver metastasis.

Abstract

Colorectal cancer (CRC) is one of the most common malignances in the gut. Liver is the most common metastasis site of CRC. This study focuses on the primary CRC and its liver metastasis, aiming to discover several liver metastasis related genes and provide therapeutic candidates. We compared gene expression patterns among the groups of normal colorectal mucosa, primary tumor and the liver metastasis using a CRC gene expression dataset. 84 genes were found to be upregulated in both primary tumor and liver metastases. Function enrichment analysis indicated that these genes are enriched in pathways such as chemotaxis, coagulation and lipid metabolism which are crucial in multi-step cancer metastasis. Gene network analysis identified several important hub genes that may be involved in carcinogenesis and liver metastasis. Then we used a validation dataset containing 562 CRC samples with detailed clinical information, to screen prognostic biomarkers for overall survival (OS) and relapse free survival (RFS). Finally, overexpression of THBS2 (thrombospondin 2), INHBB (inhibin, beta B) and BGN (biglycan) were proved to be correlated with poor OS and RFS. In conclusion, this study indicated that chemotaxis, coagulation and lipid metabolism might play critical roles in the processes of carcinogenesis and liver metastasis. THBS2, INHBB and BGN are prognostic markers and potential therapeutic targets for CRC.