title: Feasibility of Unbiased RNA Profiling of Colorectal Tumors: A Proof of Principle.
abstract: Despite recent advances in molecular profiling of colorectal cancer (CRC), as of yet this has not translated into an unbiased molecular liquid biopsy profile which can accurately screen for early CRC. In this study we depict the profile of early stage CRC as well as for advanced adenomas (AA) by combination of current molecular knowledge with microarray technology, using efficient circulating free plasma RNA purification from blood and RNA amplification technologies. We joined literature search with Affymetrix gene chip experimental procedure to draw the circulating free plasma RNA profile of colorectal cancer disease reflected in blood. The RNA panel was tested by two datasets comparing patients with CRC with healthy subjects and patients with AA to healthy subjects. For the CRC patient cohort (28 CRC cases vs. 41 healthy controls), the ROC analysis of the selected biomarker panel generated a sensitivity of 75% and a specificity of 93% for the detection of CRC using 8-gene classification model. For the AA patient cohort (28 subjects vs. 46 healthy controls), a sensitivity of 60% and a specificity of 87% were calculated using a 2-gene classification model. We have identified a panel of 8 plasma RNA markers as a preliminary panel for CRC detection and subset markers suitable for AA detection. Subjected to extensive clinical validation we suggest that this panel represents a feasible approach and a potential strategy for noninvasive early diagnosis, as a first-line screening test for asymptomatic, average-risk population before colonoscopy.
authors.affiliation: Bio-Marcare Technologies, BioPark, Jerusalem, Israel.
authors.forename: Vardit
authors.initials: V
authors.lastname: Moshayoff
authors.affiliation: Bio-Marcare Technologies, BioPark, Jerusalem, Israel.
authors.forename: Ouriel
authors.initials: O
authors.lastname: Faktor
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Laghi
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Celesti
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Peretz
authors.affiliation: Gastroenterology and Hepatology Department, Clalit Health Services, Jerusalem, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Keret
authors.affiliation: Bio-Marcare Technologies, BioPark, Jerusalem, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Cohen
authors.affiliation: Institute of Gastroenterology and Liver Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Eran
authors.identifier: http://orcid.org/0000-0001-8679-4363
authors.initials: E
authors.lastname: Israeli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics*; D005240:Feasibility Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D012334:RNA, Neoplasm / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D012372:ROC Curve
chemical_list: D012334:RNA, Neoplasm