Through integrated analyses of the transcriptional regulation, The Cancer Genome Atlas database, and 50 published microarray studies of colorectal cancer specimens, we have identified eight candidate genes that are significantly associated with the aggressive phenotype, including RPN2, HMGB1, AARS, IGFBP3, STAT1, HYOU1, NQO1 and PEA15. Among those genes, RPN2 and HMGB1 displayed higher frequencies of genomic alterations in colorectal cancer, compared to other solid tumors. This evidence concerns the gene HMGB1 and colorectal cancer.