Discovery and Validation of Circulating Biomarkers of Colorectal Adenoma by High-Depth Small RNA Sequencing

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Brian S RobertsRichard M Myers

Abstract

Purpose: Colorectal cancer is the third most common cancer worldwide, causing approximately 700,000 deaths each year. The majority of colorectal cancers begin as adenomas. Definitive screening for colorectal adenomas is currently accomplished through colonoscopy but, owing largely to costs and invasiveness, is typically limited to patient groups at higher risk by virtue of age or family history. We sought to determine if blood-based small RNA markers could detect colorectal adenoma.Experimental Design: We applied high-depth small RNA sequencing to plasma from a large (n = 189) cohort of patients, balanced for age, sex, and ancestry. Our analytical methodology allowed for the detection of both microRNAs and other small RNA species. We replicated sequencing results by qPCR on plasma samples from an independent cohort (n = 140).Results: We found several small RNA species with significant associations to colorectal adenoma, including both microRNAs and non-microRNA small RNAs. These associations were robust to correction for patient covariates, including age. Among the adenoma-associated small RNAs, two, a miR-335-5p isoform and an un-annotated small RNA, were validated by qPCR in an independent cohort. A classifier trained on meas...Continue Reading

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Citations

Nov 30, 2018·Cytopathology : Official Journal of the British Society for Clinical Cytology·Ratan Kumar GhoshPranab Dey
Jun 6, 2019·Nucleic Acids Research·Andrew A HardiganRichard M Myers
Jan 26, 2021·Cancer Biotherapy & Radiopharmaceuticals·Guo Dong HuangJun Xiong

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