// Li Zeng 1 , Kaixue Li 1 , Hong Wei 1 , Jingjing Hu 1 , Lu Jiao 1 , Juan Zhang 1 and Ying Xiong 1 1 Department of Gastroenterology, The Second People’s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China Correspondence to: Ying Xiong, email: yxiongmed@hotmail.com Keywords: colorectal cancer; epigenetic; gene methylation; prognosis Received: August 22, 2017     Accepted: November 13, 2017     Published: January 05, 2018 ABSTRACT Colorectal cancer (CRC) is the third most commonly malignance cancer worldwide. The quality of life and life expectancy of CRC survivors are seriously impacted by the recurrence after resection surgery. Therefore, there is a need to develop a reliable signature to predict the recurrence after resection surgery in CRC patients. Epigenetic alterations, especially gene methylation, have been found highly related to the metastasis of tumors. However, limited evidence is available for CRC patients. Moreover, there remains a knowledge gap of a comprehensive view of gene methylation in stage II CRC. In this study, we conducted and validated a differentially methylated 9-gene-pair prognosis signature to predict recurrence after resection surgery in stage II CRC patients. In addition, we use Univariable and Multivariable Cox regression to estimate the association between relapse free survival times in relation to each candidate gene pairs and the 9-gene-pair score. Moreover, the network analysis found 8 hub genes, including NDRG4 and BMP3 , out of all candidate genes have large degree of interactions in the protein-protein interaction network. Seven hub genes have been found associated with CRC progression. Furthermore, the function enrichment analysis suggested that differentially methylated genes were mostly enriched in the cell cycle pathway. In summary, a 9-gene-pair signature was developed and validated in this study. The signatures identified in this study have the potential to be applied in the prognosis of post-surgery recurrence in the stage II CRC patents.