Analytical Validation of the Multitarget Stool RNA Test for Colorectal Cancer Screening

J Mol Diagn. 2024 Aug;26(8):700-707. doi: 10.1016/j.jmoldx.2024.05.001. Epub 2024 Jul 10.

Abstract

The multitarget stool RNA (mt-sRNA) test (ColoSense) is a noninvasive diagnostic test that screens for colorectal cancer and advanced adenomas in average-risk individuals aged 45 years and older. The mt-sRNA test incorporates a commercially available fecal immunochemical test, concentration of eight RNA transcripts, and participant-reported smoking status. As part of the CRC-PREVENT (Colorectal Cancer and Pre-Cancerous Adenoma Non-Invasive Detection Test) clinical trial, 12 analytical validation studies were conducted to assess analytical sensitivity, linearity, precision, interfering substances, cross-reactivity, carry-over, cross-contamination, and robustness. Analytical validation of the mt-sRNA test demonstrated limit of blank, limit of detection, and limit of quantification of <0.6, <0.7, and ≤2.5 copies/μL for all markers, respectively. The mt-sRNA test demonstrated linearity between 2.5 and 2500 copies/μL, and <20% coefficient of variation, and/or ≥95% concordance with regard to precision, interfering substances, carry-over, cross-contamination, and robustness. There was no significant impact of cross-reactivity from non-colorectal cancer diseases. These data provide a framework for laboratories to complete analytical validation for RNA-based panels that require premarket approval as a class III medical device from the US Food and Drug Administration.

Publication types

  • Validation Study

MeSH terms

  • Aged
  • Biomarkers, Tumor* / genetics
  • Colorectal Neoplasms* / diagnosis
  • Colorectal Neoplasms* / genetics
  • Early Detection of Cancer* / methods
  • Feces* / chemistry
  • Female
  • Humans
  • Limit of Detection
  • Male
  • Middle Aged
  • RNA / analysis
  • RNA / genetics
  • Reproducibility of Results
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • RNA