TY - JOUR
T1 - Multitarget Stool RNA Test for Noninvasive Detection of Colorectal Neoplasias 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 - Publisher Copyright:
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.
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
VL - 12
SP - e00360
JO - Clinical and Translational Gastroenterology
JF - Clinical and Translational Gastroenterology
SN - 2155-384X
IS - 5
ER -