Abstract 4213: Stool-derived eukaryotic RNA (seRNA) assay for noninvasive detection of colorectal cancer and high-risk adenomas

Abstract

Abstract Colorectal cancer (CRC) is the second leading cause of cancer related deaths in the United States. The high mortality rate for CRC is largely attributable to the frequency of late-stage diagnoses, caused by low patient compliance with screening guidelines. A novel nucleic acid extraction method that isolates stool-derived eukaryotic RNA (seRNA) has permitted development of a colorectal cancer stool diagnostic test (CRC-SDT) that uses a fecal immunochemical test (FIT) and 11 seRNA transcripts to serve as a reliable and noninvasive screening alternative to lower mortality associated with CRC. Stool samples were obtained from 190 individuals prior to undergoing a screening colonoscopy. Patients were diagnosed as either having colorectal cancer, having high-risk adenomas (high-grade dysplasia, villous growth pattern, or >1.0cm in size), or healthy (low-risk adenomas, benign polyps, and/or no findings on a colonoscopy). FITs were obtained for each sample. Samples that had a positive FIT were considered positive for the CRC-SDT. Samples that had a negative FIT underwent seRNA isolation, library preparation (Illumina TruSeq Targeted RNA) and subsequent sequencing (Illumina NextSeq 550). A random forest model was built using 11 transcripts that were differentially expressed (log2 fold-change > 1; ANOVA p < 0.05) between diseased patients (CRC and high-risk adenomas) relative to the healthy cohort. Internal 10-fold cross-validation was performed for the training set and a receiver operating characteristic (ROC) area under the curve (AUC) determined model accuracy for cancer and high-risk adenomas relative to the healthy cohort. Model predictions for an independent hold-out test set were used to determine model accuracy for colorectal cancer and high-risk adenomas. Internal cross-validation for 154 samples attained a ROC AUC of 0.82. The trained model was employed on the independent hold-out test set of 36 samples and model predictions were compared to colonoscopy results. The model attained a 100% sensitivity for CRC (n = 7), a 60% sensitivity for high-risk adenomas (n = 5), and an 88% combined specificity for the healthy cohort (n = 24). CRC-SDT uses 12 biomarkers (FIT and expression from 11 seRNA transcripts) to accurately detect CRC and high-risk adenomas. Use of seRNA biomarkers dramatically improves detection of high-risk adenomas relative to existing noninvasive screening methods for CRC. Citation Format: Erica K. Barnell, Yiming Kang, Katie M. Campbell, Kimberly R. Kruse, Andrew R. Barnell, Elizabeth M. Wurtzler. Stool-derived eukaryotic RNA (seRNA) assay for noninvasive detection of colorectal cancer and high-risk adenomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4213.