Open AccessPreinvasive colorectal lesion transcriptomes correlate with endoscopic morphology (polypoid vs. nonpolypoid)
Author(s) -
Cattaneo Elisa,
Laczko Endre,
Buffoli Federico,
Zorzi Fausto,
Bianco Maria Antonia,
Menigatti Mirco,
Bartosova Zdena,
Haider Ritva,
Helmchen Birgit,
SabatesBellver Jacob,
Tiwari Amit,
Jiricny Josef,
Marra Giancarlo
Publication year - 2011
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201100141
Subject(s) - dysplasia , lesion , colonoscopy , colorectal cancer , pathology , biology , transcriptome , histology , gene , gene expression , cancer , medicine , genetics
Improved colonoscopy is revealing precancerous lesions that were frequently missed in the past, and ∼30% of those detected today have nonpolypoid morphologies ranging from slightly raised to depressed. To characterize these lesions molecularly, we assessed transcription of 23,768 genes in 42 precancerous lesions (25 slightly elevated nonpolypoid and 17 pedunculated polypoid), each with corresponding samples of normal mucosa. Nonpolypoid versus polypoid morphology explained most gene expression variance among samples; histology, size, and degree of dysplasia were also linked to specific patterns. Expression changes in polypoid lesions frequently affected cell‐cycling pathways, whereas cell‐survival dysregulation predominated in nonpolypoid lesions. The latter also displayed fewer and less dramatic expression changes than polypoid lesions. Paradigmatic of this trend was progressive loss through the normal > nonpolypoid > polypoid > cancer sequence of TMIGD1 mRNA and protein. This finding, along with TMIGD1 protein expression patterns in tissues and cell lines, suggests that TMIGD1 might be associated with intestinal‐cell differentiation. We conclude that molecular dysregulation in slightly elevated, nonpolypoid, precancerous colorectal lesions may be somewhat less severe than that observed in classic adenomatous polyps.