Plasma microRNAs – novel markers for the detection of colonic polyps and their progression to colorectal cancer
thesisposted on 2017-10-27, 14:14 authored by Ajay M. Verma
Introduction: Bowel cancer screening programme (BCSP) subjects aged 55 are screened by bowel scope sigmoidoscopy, aged 60-75 by faecal occult blood testing (FOBt - positive subjects undergo colonoscopy). Whilst effective, FOBt lacks high sensitivity, specificity and accuracy, >90% sigmoidoscopies and 50% colonoscopies are normal or non-adenoma diagnosis. Endoscopy screening is invasive, resource intensive and can cause harm. Uptake of FOBt and bowel scope is <60%. A blood based screening test is an appealing alternative. Methods: We investigated microRNAs (miRs) – short non-coding RNA molecules as potential biomarkers. 181 FOBt+ subjects and 29 others undergoing endoscopy were recruited – 128 males, 82 females. 117 with polyps (99 adenomas), 12 colorectal cancer, 81 controls. RNA was extracted from plasma and processed. Pooled groups were analysed using microarray assay cards. Ten candidate miRs 19a, 98, 146b, 186, 331–5p, 452, 625, 222#, 664 and 1247 were identified. Cases were analysed for candidate microRNA expression by quantitative polymerase chain reaction. Results: Candidate miRs showed significant levels of expression in subjects with adenomas on T-testing. miRs 98 & 19a; p=<0.05, miRs 146b, 625; p=<0.01, miR-186 p=<0.001. The results were more significant for male subjects. Receiver operated characteristic curves for miR-panels showed: Polyps in male subjects, miRs 98, 186, 452; sensitivity 0.600, specificity 0.872. Adenomas in male subjects, miRs 98, 186, 452. Sensitivity 0.606/0.591, specificity 0.875/0.900. Polyps with diverticulosis/haemorrhoids; miRs 186, 452, 331–5p; sensitivity 0.600/0.633, specificity 0.889/0.867. Adenomas with diverticulosis/haemorrhoids; miRs 625, 452, 331–5p; sensitivity 0.714, specificity 0.864. Conclusion: This study suggest plasma microRNAs are potential screening biomarkers for male subjects with colorectal polyps, adenomas and subjects with adenomas and diverticulosis/haemorrhoids. Further study is needed to validate these exciting findings.
Supervisor(s)Pringle, Howard; Singh, Baljit
Date of award2017-10-04
Author affiliationDepartment of Cancer Studies & Molecular Medicine
Awarding institutionUniversity of Leicester