Multitarget Stool RNA Test for Noninvasive Detection of Colorectal Neoplasias in a Multicenter, Prospective, and Retrospective Cohort

Erica K. Barnell, Yiming Kang, Andrew R. Barnell, Kimberly R. Kruse, Jared Fiske, Zachary R. Pittz, Adnan R. Khan, Thomas A. Huebner, Faith L. Holmes, Malachi Griffith, Obi L. Griffith, Aadel A. Chaudhuri, Elizabeth M. Wurtzler

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)e00360
JournalClinical and Translational Gastroenterology
Volume12
Issue number5
DOIs
StatePublished - May 24 2021

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