AIM: To investigate the differently expressed genes in human colorectal adenocarcinoma.METHODS: The integrated approach for gene expression profiling that couples suppression subtractive hybridization, high-throughput cDNA array, sequencing,bioinformatics analysis, and reverse transcriptase realtime quantitative polymerase chain reaction (PCR)was carried out. A set of cDNA clones including 1260SSH inserts amplified by PCR was arrayed using robotic printing. The cDNA arrays were hybridized with florescent-labeled probes prepared from RNA of human colorectal adenocarcinoma (HCRAC) and normal colorectal tissues.RESULTS: A total of 86 genes were identified, 16 unknown genes and 70 known genes. The transcription factor Sox9 influencing cell differentiation was downregulated. At the same time, Heat shock protein 10 KDis downregulated and Calmoulin is up-regulated.CONCLUSION: Downregulation of heat shock protein 10 KD lost its inhibition of Ras, and then attenuated the Ras GTPase signaling pathway, increased cell proliferation and inhibited cell apoptosis. Down-regulated transcription factor Sox9 influences cell differentiation and cell-specific gene expression. Down-regulated Sox9 also decreases its binding to calmodulin, accumulates calmodulin as receptor-activated kinase and phosphorylase kinase due to the activation of PhK.