TY - JOUR
T1 - Multitarget Stool RNA Test for Noninvasive Detection of Colorectal Neoplasia in a Multicenter, Prospective, and Retrospective Cohort
AU - Barnell, Erica K.
AU - Kang, Yiming
AU - Barnell, Andrew R.
AU - Kruse, Kimberly R.
AU - Fiske, Jared
AU - Pittz, Zachary R.
AU - Khan, Adnan R.
AU - Huebner, Thomas A.
AU - Holmes, Faith L.
AU - Griffith, Malachi
AU - Griffith, Obi L.
AU - Chaudhuri, Aadel A.
AU - Wurtzler, Elizabeth M.
N1 - Funding Information:
Financial support: This research was funded by Geneoscopy Inc. (St. Louis, MO), a molecular diagnostics company. A. Chaudhuri is supported by the V Foundation V Scholar Award, the Alvin Siteman Cancer Research Fund, and the NCI K08CA238711 Career Development Award. M. Griffith is supported by the National Human Genome Research Institute under award number R00HG007940. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Funding Information:
We thank the participants and their families for their selfless and generous contributions to science. We greatly appreciate the Geneoscopy Quality Team (Ian Rappold and Matthew Schnell) and the Geneoscopy Science/Software Team (Ben Wedeking, Brett Gleason, and Beekey Cheung) for their contribution to the maintenance of high data integrity. Finally, this research was made possible by the individuals at TynanDx (Katherine Tynan), at Elligo Health Research Team (Tyler Payne, Kellie Esinhart, Paul Couey, Beverly Cerda, Kacey Christian, Jackie Bodmer, Hicham Fayad, Rob Shepler, Matt Tibby, Pablo Alvarez, Patrick Riordan, Dan Hedges, Kristen Amarone, Anita Suri, Deborah Svochak, Valeria Apodaca, and Leviette Sigala), and at 83Bar (Karen Wallingford, Alex Hilderbrand, Mike Zangrilli, Amanda Westcott, Meredyth Glass, and Sara Shissler). We also thank our advisors for their contribution to this work (Liz Lison, Mike Wood, and Jon Harrington).
Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/5/24
Y1 - 2021/5/24
N2 - INTRODUCTION:Effective colorectal cancer (CRC) prevention and screening requires sensitive detection of all advanced neoplasias (CRC and advanced adenomas [AA]). However, existing noninvasive screening approaches cannot accurately detect adenomas with high sensitivity.METHODS:Here, we describe a multifactor assay (RNA-FIT test) that combines 8 stool-derived eukaryotic RNA biomarkers, patient demographic information (smoking status), and a fecal immunochemical test (FIT) to sensitively detect advanced colorectal neoplasias and other non-advanced adenomas in a 1,305-patient, average-risk, prospective cohort. This cohort was supplemented with a 22-patient retrospective cohort consisting of stool samples obtained from patients diagnosed with AA or CRC before treatment or resection. Participants within these cohorts were evaluated with the RNA-FIT assay and an optical colonoscopy. RNA-FIT test results were compared with colonoscopy findings.RESULTS:Model performance was assessed through 5-fold internal cross-validation of the training set (n = 939) and by using the model on a hold out testing set (n = 388). When used on the hold out testing set, the RNA-FIT test attained a 95% sensitivity for CRC (n = 22), 62% sensitivity for AA (n = 52), 25% sensitivity for other non-AA (n = 139), 80% specificity for hyperplastic polyps (n = 74), and 85% specificity for no findings on a colonoscopy (n = 101).DISCUSSION:The RNA-FIT assay demonstrated clinically relevant detection of all grades of colorectal neoplasia, including carcinomas, AAs, and ONAs. This assay could represent a noninvasive option to screen for both CRC and precancerous adenomas.
AB - INTRODUCTION:Effective colorectal cancer (CRC) prevention and screening requires sensitive detection of all advanced neoplasias (CRC and advanced adenomas [AA]). However, existing noninvasive screening approaches cannot accurately detect adenomas with high sensitivity.METHODS:Here, we describe a multifactor assay (RNA-FIT test) that combines 8 stool-derived eukaryotic RNA biomarkers, patient demographic information (smoking status), and a fecal immunochemical test (FIT) to sensitively detect advanced colorectal neoplasias and other non-advanced adenomas in a 1,305-patient, average-risk, prospective cohort. This cohort was supplemented with a 22-patient retrospective cohort consisting of stool samples obtained from patients diagnosed with AA or CRC before treatment or resection. Participants within these cohorts were evaluated with the RNA-FIT assay and an optical colonoscopy. RNA-FIT test results were compared with colonoscopy findings.RESULTS:Model performance was assessed through 5-fold internal cross-validation of the training set (n = 939) and by using the model on a hold out testing set (n = 388). When used on the hold out testing set, the RNA-FIT test attained a 95% sensitivity for CRC (n = 22), 62% sensitivity for AA (n = 52), 25% sensitivity for other non-AA (n = 139), 80% specificity for hyperplastic polyps (n = 74), and 85% specificity for no findings on a colonoscopy (n = 101).DISCUSSION:The RNA-FIT assay demonstrated clinically relevant detection of all grades of colorectal neoplasia, including carcinomas, AAs, and ONAs. This assay could represent a noninvasive option to screen for both CRC and precancerous adenomas.
UR - http://www.scopus.com/inward/record.url?scp=85106926444&partnerID=8YFLogxK
U2 - 10.14309/ctg.0000000000000360
DO - 10.14309/ctg.0000000000000360
M3 - Article
C2 - 34029233
AN - SCOPUS:85106926444
SN - 2155-384X
VL - 12
SP - E00360
JO - Clinical and Translational Gastroenterology
JF - Clinical and Translational Gastroenterology
IS - 5
ER -