In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 4213-4213
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 & gt;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 & gt; 1; ANOVA p & lt; 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.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2019-4213
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2019
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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