TY - JOUR T1 - Stool-derived eukaryotic RNA biomarkers for detection of high-risk adenomas JF - bioRxiv DO - 10.1101/534412 SP - 534412 AU - Erica Barnell AU - Yiming Kang AU - Andrew Barnell AU - Katie Campbell AU - Kimberly R. Kruse AU - Elizabeth M. Wurtzler AU - Malachi Griffith AU - Aadel A. Chaudhuri AU - Obi L. Griffith Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/01/29/534412.abstract N2 - Background and aims Colorectal cancer (CRC) is the second leading cause of cancer related deaths in the United States. Mortality is largely attributable to low patient compliance with screening and a subsequent high frequency of late-stage diagnoses. Noninvasive methods, such as stool- or blood-based diagnostics could improve patient compliance, however, existing techniques cannot adequately detect high-risk adenomas (HRAs) and early-stage CRC.Methods Here we apply cancer profiling using amplicon sequencing of stool-derived eukaryotic RNA for 275 patients undergoing prospective CRC screening. A training set of 154 samples was used to build a random forest model that included 4 feature types (differentially expressed amplicons, total RNA expression, demographic information, and fecal immunochemical test results). An independent hold out test set of 121 patients was used to assess model performance.Results When applied to the 121-patient hold out test set, the model attained a receiver operating characteristic (ROC) area under the curve (AUC) of 0.94 for CRC and a ROC AUC of 0.87 for CRC and HRAs. In aggregate, the model achieved a 91 % sensitivity for CRC and a 73% sensitivity for HRAs at an 89% specificity for all other findings (medium-risk adenomas, low-risk adenomas, benign polyps, and no findings on a colonoscopy).Conclusion Collectively, these results indicate that in addition to early CRC detection, stool-derived biomarkers can accurately and noninvasively identify HRAs, which could be harnessed to prevent CRC development for asymptomatic, average-risk patients.AbbreviationsAUCarea under the curve ANOVA analysis of varianceCRCcolorectal cancerDEdifferentially expressedFCfold-changeFITfecal immunochemical testHRAhigh-risk adenomaLRAlow-risk adenomaMRAmedium-risk adenomaNPVnegative predictive valuePPVpositive predictive valueROCreceiver operating characteristicseRNAstool-derived eukaryotic RNA ER -