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

Clin Transl Gastroenterol. 2021 May 24;12(5):e00360. doi: 10.14309/ctg.0000000000000360.


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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Colorectal Neoplasms / diagnosis*
  • Early Detection of Cancer / methods
  • Feces / chemistry*
  • Female
  • Humans
  • Immunochemistry / methods*
  • Male
  • Mass Screening / methods
  • Middle Aged
  • Prospective Studies
  • RNA / analysis*
  • Retrospective Studies
  • Sensitivity and Specificity
  • Smoking
  • Socioeconomic Factors


  • Biomarkers, Tumor
  • RNA