Clinical Performance of a Stool RNA Assay for Early Detection of Precancerous Adenomas and Colorectal Cancer

ABSTRACT: Background and Aims: RNA biomarkers derived from sloughed enterocytes would provide an ideal, non-invasive method for early detection of colorectal cancer (CRC) and precancerous adenomas. To realize this goal, a highly reliable method to isolate preserved human RNA from stool samples is needed. Here we develop a protocol to identify RNA biomarkers associated with CRC to assess the use of these biomarkers for noninvasive screening of disease. Methods: Stool samples were collected from 454 patients prior to a colonoscopy. A nucleic acid extraction protocol was developed to isolate human RNA from 330 stool samples and transcript abundances were estimated by microarray analysis. This 330-patient cohort was split into a training set of 265 individuals to develop a machine learning model and a testing set of 65 individuals to determine the model’s ability to detect colorectal neoplasms. Results: Analysis of the transcriptome from 265 individuals identified 200 transcript clusters as differentially expressed (p<0.03). These transcripts were used to build a Support Vector Machine (SVM) based model to classify 65 individuals within the testing set. This SVM algorithm attained a 95% sensitivity for precancerous adenomas and a 65% sensitivity for CRC (stage I-IV). The machine learning algorithm attained a specificity of 59% for healthy individuals and an overall accuracy of 72.3%. Conclusions: We developed an RNA-based neoplasm detection model that is sensitive for CRC and precancerous adenomas. The model allows for non-invasive assessment of tumors and could potentially be used to provide clinical guidance for individuals within the screening population for colorectal cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE99573 | GEO | 2019/02/25

REPOSITORIES: GEO