1. Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
2. Desautels Faculty of Management, McGill University, Montreal, Quebec, H3A 1G5, Canada.
3. Schulich School of Music, McGill University, Montreal, Quebec, H3A 1E3, Canada.
4. Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center, Montreal, Quebec, H2X0A9, Canada.
5. State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China.
6. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
7. Department of Mathematics, Nanjing University, 210023, China.
8. Department of Pathology, Research Institute of McGill University Health Center, Montreal, Quebec, H4A 3J1, Canada
Background: Sensitive and specific non-invasive biomarkers are urgently needed in order to improve the survival of patients with pancreatic ductal adenocarcinoma (PDAC), which is the fourth leading cause of cancer-related death. We aim to identify serum hub miRNAs as potential diagnostic and prognostic biomarkers for PDAC.
Methods: A total of 2578 serum miRNA expression data from 88 PDAC patients and 19 healthy subjects were downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was constructed and significant modules were extracted from the network by WGCNA R package. Network modules and hub miRNAs closely related to PDAC were identified. The prognostic value of hub miRNAs was assessed by Kaplan-Meier overall survival analysis.
Results: Two modules strongly associated with PDAC were identified by WGCNA, which were labeled as turquoise and brown respectively. Within each module, twenty hub miRNAs were found. At the functional level, turquoise module was mainly associated with tumorigenesis pathways such as P53 and WNT signaling pathway, while the brown module was mostly related to the pathways of cancer such as RNA transport and MAPK signaling pathway. Utilizing overall survival analyses, five “real” miRNAs were able to stratify PDAC patients into low-risk and high-risk groups.
Conclusions: The association of specific Hub miRNAs with the development of pancreatic cancer was established by WGCNA analysis. Five miRNAs (mir-16-2-3p, mir-890, mir-3201, mir-602, and mir-877) were identified as potential diagnostic and prognostic biomarkers for PDAC.
Keywords: Hub miRNAs, miRNAs, pancreatic ductal adenocarcinoma