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Published on: May 21, 2019
Investigating MicroRNA Expression Profiles in Pancreatic Cystic Neoplasms
Linda S Lee1, Anna E Szafranska-Schwarzbach2, Dennis Wylie2
11] Center for Pancreatic Disease, Brigham and Women's Hospital, Boston, Massachusetts, USA [2] Interdisciplinary Management of Pancreatic Cystic Tumors (IMPACT) Clinic, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Objectives:
Current diagnostic tools for pancreatic cysts fail to reliably differentiate mucinous from nonmucinous cysts. Reliable biomarkers are needed. MicroRNAs (miRNA) may offer insights into pancreatic cysts. Our aims were to (1) identify miRNAs that distinguish benign from both premalignant cysts and malignant pancreatic lesions using formalin-fixed, paraffin-embedded (FFPE) pathology specimens; (2) identify miRNAs that distinguish mucinous cystic neoplasm (MCN) from branch duct-intraductal papillary mucinous neoplasm (BD-IPMN).
Methods:
A total of 69 FFPE pancreatic specimens were identified: (1) benign (20 serous cystadenoma (SCA)), (2) premalignant (10 MCN, 10 BD-IPMN, 10 main duct IPMN (MD-IPMN)), and (3) malignant (19 pancreatic ductal adenocarcinoma (PDAC)). Total nucleic acid extraction was performed followed by miRNA expression profiling of 378 miRNAs interrogated using TaqMan MicroRNA Arrays Pool A and verification of candidate miRNAs. Bioinformatics was used to generate classifiers.
Results:
MiRNA profiling of 69 FFPE specimens yielded 35 differentially expressed miRNA candidates. Four different 4-miRNA panels differentiated among the lesions: one panel separated SCA from MCN, BD-IPMN, MD-IPMN, and PDAC with sensitivity 85% (62, 97), specificity 100% (93, 100), a second panel distinguished MCN from SCA, BD-IPMN, MD-IPMN, and PDAC with sensitivity and specificity 100% (100, 100), a third panel differentiated PDAC from IPMN with sensitivity 95% (76, 100) and specificity 85% (72, 96), and the final panel diagnosed MCN from BD-IPMN with sensitivity and specificity approaching 100%.
Conclusions:
MiRNA profiling of surgical pathology specimens differentiates serous cystadenoma from both premalignant pancreatic cystic neoplasms and PDAC and MCN from BD-IPMN.
Insights
MicroRNA (miRNA) profiling of pancreatic cysts accurately distinguishes benign from malignant lesions and mucinous cystic neoplasm from branch duct-intraductal papillary mucinous neoplasm. This approach offers a novel biomarker for pancreatic cyst diagnosis.
Area of Science:
- Gastroenterology and Hepatology
- Oncology
- Molecular Biology
Background:
- Current diagnostic methods struggle to differentiate mucinous from nonmucinous pancreatic cysts.
- Reliable biomarkers are crucial for accurate diagnosis and management of pancreatic cystic lesions.
- MicroRNAs (miRNAs) show potential as diagnostic biomarkers in various cancers.
Purpose of the Study:
- To identify miRNAs that distinguish benign pancreatic cysts from premalignant and malignant lesions using FFPE specimens.
- To identify miRNAs that differentiate mucinous cystic neoplasm (MCN) from branch duct-intraductal papillary mucinous neoplasm (BD-IPMN).
Main Methods:
- Analysis of 69 FFPE pancreatic specimens, including benign, premalignant, and malignant lesions.
- miRNA expression profiling of 378 miRNAs using TaqMan MicroRNA Arrays.
- Bioinformatic analysis to develop miRNA-based diagnostic classifiers.
Main Results:
- 35 differentially expressed miRNA candidates were identified.
- Four distinct 4-miRNA panels demonstrated high accuracy in differentiating lesion types.
- Panels achieved high sensitivity and specificity in distinguishing serous cystadenoma (SCA), MCN, IPMN, and pancreatic ductal adenocarcinoma (PDAC).
Conclusions:
- miRNA profiling of surgical pathology specimens can reliably differentiate benign pancreatic cysts from premalignant and malignant neoplasms.
- Specific miRNA panels can distinguish MCN from BD-IPMN with near-perfect accuracy.
- miRNAs represent promising biomarkers for improved pancreatic cyst diagnosis.
