A Plasma MicroRNA Panel for Detection of Colorectal Adenomas A Step Toward More Precise Screening for Colorectal Cancer

作者：Kanaan Ziad; Roberts Henry; Eichenberger M Robert; Billeter Adrian; Ocheretner Gairy; Pan Jianmin; Rai Shesh N; Jorden Jeffery; Williford Anna; Galandiuk Susan^*

来源：Annals of Surgery, 2013, 258(3): 400-408.

DOI：10.1097/SLA.0b013e3182a15bcc

• adenomas
• biomarker
• colorectal cancer
• microRNA
• plasma

Objective: The main objective of this study was to investigate the potential use of circulating microRNAs (miRNAs) as biomarkers of colorectal (CR) adenomas. %26lt;br%26gt;Background: Detection of precancerous lesions such as CR adenoma is a key to reduce CR cancer (CRC) mortality. There is a great need for accurate, noninvasive biomarkers for detection of CR adenoma and CRC. MiRNAs are non-protein-coding RNAs that regulate gene expression. Our prior work investigated the dysregulation of 5 plasma miRNAs in CRC patients. As intended, we undertook a more comprehensive plasma-miRNA screening study in patients with CR adenoma and CRC. %26lt;br%26gt;Methods: We screened for 380 plasma-miRNAs using microfluidic array technology (Applied BioSystems) in a screening cohort of 12 healthy controls, 9 patients with CR adenomas, and 20 patients with CRC. A panel of the most dysregulated miRNAs (P %26lt; 0.05, False Discovery Rate: 5%) was then validated in a blinded cohort of 26 healthy controls, 16 patients with large adenomas, and 45 patients with CRC. %26lt;br%26gt;Results: A panel of 8 plasma miRNAs (miR-532-3p, miR-331, miR-195, miR-17, miR-142-3p, miR-15b, miR-532, and miR-652) distinguished polyps from controls with high accuracy [area under curve (AUC)= 0.868 (95% confidence interval [CI]: 0.76-0.98)]. In addition, a panel of 3 plasma miRNAs (miR-431, miR-15b, and miR-139-3p) distinguished Stage IV CRC from controls with an [ AUC = 0.896 (95% CI: 0.78-1.0)]. Receiver-operating-characteristic curves of miRNA panels for all CRC versus controls and polyps versus all CRC showed AUC values of 0.829 (95% CI: 0.73-0.93) and 0.856 (95% CI: 0.75-0.97), respectively. %26lt;br%26gt;Conclusions: Plasma miRNAs are reliable, noninvasive, and inexpensive markers for CR adenomas. This miRNA panel warrants study in larger cohorts. Plasma-based assays could provide better screening compliance compared to fecal occult blood or endoscopic screening.

• 出版日期2013-9