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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.
AuthorsVardit Moshayoff, Ouriel Faktor, Luigi Laghi, Giuseppe Celesti, Tamar Peretz, Dan Keret, Dana Cohen, Eran Israeli
JournalPloS one (PLoS One) Vol. 11 Issue 7 Pg. e0159522 ( 2016) ISSN: 1932-6203 [Electronic] United States
PMID27441409 (Publication Type: Journal Article)
Chemical References
  • RNA, Neoplasm
Topics
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Case-Control Studies
  • Cohort Studies
  • Colorectal Neoplasms (blood, genetics)
  • Feasibility Studies
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • RNA, Neoplasm (blood, genetics, metabolism)
  • ROC Curve

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