title: Preinvasive colorectal lesion transcriptomes correlate with endoscopic morphology (polypoid vs. nonpolypoid).
abstract: 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.
authors.affiliation: Institute of Molecular Cancer Research, University of Zurich, Switzerland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cattaneo
authors.forename: Endre
authors.initials: E
authors.lastname: Laczko
authors.forename: Federico
authors.initials: F
authors.lastname: Buffoli
authors.forename: Fausto
authors.initials: F
authors.lastname: Zorzi
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Bianco
authors.forename: Mirco
authors.initials: M
authors.lastname: Menigatti
authors.forename: Zdena
authors.initials: Z
authors.lastname: Bartosova
authors.forename: Ritva
authors.initials: R
authors.lastname: Haider
authors.forename: Birgit
authors.initials: B
authors.lastname: Helmchen
authors.forename: Jacob
authors.initials: J
authors.lastname: Sabates-Bellver
authors.forename: Amit
authors.initials: A
authors.lastname: Tiwari
authors.forename: Josef
authors.initials: J
authors.lastname: Jiricny
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Marra
mesh_terms: D018256:Adenomatous Polyps / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D025341:Principal Component Analysis
chemical_list: D008562:Membrane Glycoproteins; C561473:TMIGD1 protein, human