Sporadic early-onset colon cancer expresses unique molecular features.

BACKGROUND: The overall incidence of colon cancer (CC) has steadily declined in the last decades but has increased in patients under age 50 y. The etiology of early-onset (EO) CC is not understood. The aim of this study was to elucidate gene expression patterns in EOCC and show its uniqueness compared to late-onset (LO) disease. METHODS: Two cohorts of patients with sporadic CC were identified. Tumors and matching noninvolved tissues from six EOCC patients (<50) and six late-onset colon cancers (LOCC) patients (>65) were obtained from pathology archives. De-paraffinized tissues were macrodissected from FFPE sections, RNA isolated, and used for expression profiling of 770 cancer-related genes representing 13 canonical pathways. RESULTS: Among 770 genes assayed, changes in expression levels of 93 genes were statistically significant between EOCC and matching noninvolved tissues. There were also significant differences in expression levels of 118 genes between LOCC and matching noninvolved tissues. Detailed comparative gene expression analysis between EOCC and LOCC normalized to their matching noninvolved tissues revealed that changes in expression of 88 genes were unique to EOCC using the cutoff criteria of expression levels difference >2 fold and P value <0.01. From these differentially expressed genes specific to EOCC, 28 genes were upregulated and 60 genes downregulated. At the pathway level, RAS, MAPK, WNT, and DNARepair pathways were similarly deregulated in both age groups, whereas PI3K-AKT signaling was more specific to EOCC and cell cycle pathway to LOCC. CONCLUSIONS: These results suggest that sporadic EOCC is characterized by distinct molecular events compared to LOCC.