Gene Expression Differences between Colon and Rectum Tumors

Abstract

Purpose: Colorectal cancer studies typically include both colon and rectum tumors as a common entity, though this assumption is controversial and only minor differences have been reported at the molecular and epidemiologic level. We conducted a molecular study based on gene expression data of tumors from colon and rectum to assess the degree of similarity between these cancer sites at transcriptomic level.Experimental Design: A pooled analysis of 460 colon tumors and 100 rectum tumors from four data sets belonging to three independent studies was conducted. Microsatellite instable tumors were excluded as these are known to have a different expression profile and have a preferential proximal colon location. Expression differences were assessed with linear models, and significant genes were identified using adjustment for multiple comparisons.Results: Minor differences at a gene expression level were found between tumors arising in the proximal colon, distal colon, or rectum. Only several HOX genes were found to be associated with tumor location. More differences were found between proximal and distal colon than between distal colon and rectum.Conclusions: Microsatellite stable colorectal cancers do not show major transcriptomic differences for tumors arising in the colon or rectum. The small but consistent differences observed are largely driven by the HOX genes. These results may have important implications in the design and interpretation of studies in colorectal cancer. Clin Cancer Res; 17(23); 7303-12. Ó2011 AACR.

Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue

“…This is consistent with clinical practice, where colon and rectal cancers are treated as distinct entities (47), and a growing body of evidence that associations between dietary patterns, chemoprotective nonsteroidal anti-inflammatory drugs (NSAIDs), and CRC risk differ across anatomic subsites (21,37). In contrast, a recent comprehensive molecular characterization of human colon and rectal cancer demonstrated that after excluding hypermutated cancers, colon and rectal cancers appear to have similar patterns of genomic alteration (40).…”

“…Of the top 20, five were HOX genes (HOXA3, HOXD9, HOXD10, HOXD11, and HOXD-AS2, a HOXD cluster anti- sense RNA) with all but HOXA3 expressed at higher levels in sigmoid colon. This is noteworthy, because several HOX genes have been associated with tumor location (47). In addition, HOX overexpression contributes to stem cell overpopulation that drives colon tumorigenesis (6).…”

“…In contrast, a recent comprehensive molecular characterization of human colon and rectal cancer demonstrated that after excluding hypermutated cancers, colon and rectal cancers appear to have similar patterns of genomic alteration (40). In addition, although several molecular profiles have been used to predict prognosis in CRC patients (4,17,36), it now appears that only minor differences at the gene expression level are detected in tumors arising in the proximal colon, distal colon and rectum (47).…”

Differential expression of carbohydrate antigen 19-9 in human colorectal cancer: A comparison with colon and rectal cancers

“…Previous studies indicated that colon and rectal cancer were similar but different types of cancer (14,16,24,26). Therefore, we continued our study by analyzing colon and rectal cancer as matched pairs (Table IV and Fig.…”

“…The CIN pathway is far more common in rectal compared to colon cancers (24,25). In addition, several homeobox genes were found to be associated with tumor location (26). A different number of mutations induce varying mechanisms of oncogenesis in colon and rectal cancer.…”