Background & Aims: Colorectal cancer incidence and deaths are reduced by the detection and removal of early-stage,\ntreatable neoplasia but we lack proven biomarkers sensitive for both cancer and pre-invasive adenomas. The aims of this\nstudy were to determine if adenomas and cancers exhibit characteristic patterns of biomarker expression and to explore\nwhether a tissue-discovered (and validated) biomarker is differentially expressed in the plasma of patients with colorectal\nadenomas or cancer.\nMethods: Candidate RNA biomarkers were identified by oligonucleotide microarray analysis of colorectal specimens (222\nnormal, 29 adenoma, 161 adenocarcinoma and 50 colitis) and validated in a previously untested cohort of 68 colorectal\nspecimens using a custom-designed oligonucleotide microarray. One validated biomarker, KIAA1199, was assayed using\nqRT-PCR on plasma extracted RNA from 20 colonoscopy-confirmed healthy controls, 20 patients with adenoma, and 20 with\ncancer.\nResults: Genome-wide analysis uncovered reproducible gene expression signatures for both adenomas and cancers\ncompared to controls. 386/489 (79%) of the adenoma and 439/529 (83%) of the adenocarcinoma biomarkers were validated\nin independent tissues. We also identified genes differentially expressed in adenomas compared to cancer. KIAA1199 was\nselected for further analysis based on consistent up-regulation in neoplasia, previous studies and its interest as an\nuncharacterized gene. Plasma KIAA1199 RNA levels were significantly higher in patients with either cancer or adenoma (31/\n40) compared to neoplasia-free controls (6/20).\nConclusions: Colorectal neoplasia exhibits characteristic patterns of gene expression. KIAA1199 is differentially expressed in\nneoplastic tissues and KIAA1199 transcripts are more abundant in the plasma of patients with either cancer or adenoma\ncompared to controls.
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