Differential MicroRNA Signatures in the Pathogenesis of Barrett's Esophagus. Clin Transl Gastroenterol 2020 Jan;11(1):e00125
Date
01/15/2020Pubmed ID
31934893Pubmed Central ID
PMC7056055DOI
10.14309/ctg.0000000000000125Scopus ID
2-s2.0-85078691824 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
OBJECTIVES: Barrett's esophagus (BE) is the precursor lesion and a major risk factor for esophageal adenocarcinoma (EAC). Although patients with BE undergo routine endoscopic surveillance, current screening methodologies have proven ineffective at identifying individuals at risk of EAC. Since microRNAs (miRNAs) have potential diagnostic and prognostic value as disease biomarkers, we sought to identify an miRNA signature of BE and EAC.
METHODS: High-throughput sequencing of miRNAs was performed on serum and tissue biopsies from 31 patients identified either as normal, gastroesophageal reflux disease (GERD), BE, BE with low-grade dysplasia (LGD), or EAC. Logistic regression modeling of miRNA profiles with Lasso regularization was used to identify discriminating miRNA. Quantitative reverse transcription polymerase chain reaction was used to validate changes in miRNA expression using 46 formalin-fixed, paraffin-embedded specimens obtained from normal, GERD, BE, BE with LGD or HGD, and EAC subjects.
RESULTS: A 3-class predictive model was able to classify tissue samples into normal, GERD/BE, or LGD/EAC classes with an accuracy of 80%. Sixteen miRNAs were identified that predicted 1 of the 3 classes. Our analysis confirmed previous reports indicating that miR-29c-3p and miR-193b-5p expressions are altered in BE and EAC and identified miR-4485-5p as a novel biomarker of esophageal dysplasia. Quantitative reverse transcription polymerase chain reaction validated 11 of 16 discriminating miRNAs.
DISCUSSION: Our data provide an miRNA signature of normal, precancerous, and cancerous tissue that may stratify patients at risk of progressing to EAC. We found that serum miRNAs have a limited ability to distinguish between disease states, thus limiting their potential utility in early disease detection.
Author List
Craig MP, Rajakaruna S, Paliy O, Sajjad M, Madhavan S, Reddy N, Zhang J, Bottomley M, Agrawal S, Kadakia MPAuthor
Srivats Madhavan MBBS Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdenocarcinomaAdult
Aged
Aged, 80 and over
Barrett Esophagus
Case-Control Studies
Discriminant Analysis
Esophageal Neoplasms
Esophagus
Gastroesophageal Reflux
Humans
Logistic Models
MicroRNAs
Middle Aged
Neoplasm Grading
Reverse Transcriptase Polymerase Chain Reaction
Transcriptome