Abstract
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is considered as one of the most aggressive cancers lacking efficient early detection biomarkers. Circulating miRNAs are now being considered to have potency to be used as diagnostic and prognostic biomarkers in different diseases as well as cancers. In case of cancer, a fraction of the circulating miRNAs is actually derived from the tumour tissue. This fraction would function as stable biomarker for the disease and also would contribute to the understanding of the disease development. There are not many studies exploring this aspect in pancreatic cancer and even there is not much overlap of results between existing studies. METHODS: In order to address that gap, we performed a miRNA microarray analysis to identify differentially expressed circulating miRNAs between PDAC patients and normal healthy individuals and also found two more similar datasets to perform a meta-analysis using a total of 182 PDAC patients and 170 normal, identifying a set of miRNAs significantly altered in patient serum. Next, we found five datasets studying miRNA expression profile in tumour tissues of PDAC patients as compared to normal pancreas and performed a second meta-analysis using data from a total of 183 pancreatic tumour and 47 normal pancreas to detect significantly deregulated miRNAs in pancreatic carcinoma. Comparison of these two lists and subsequent search for their target genes which were also deregulated in PDAC in inverse direction to miRNAs was done followed by investigation of their role in disease development. RESULTS: We identified 21 miRNAs altered in both pancreatic tumour tissue and serum. While deciphering the functions of their target genes, we characterized key miR-Gene interactions perturbing the biological pathways. We identified important cancer related pathways, pancreas specific pathways, AGE-RAGE signaling, prolactin signaling and insulin resistance signaling pathways among the most affected ones. We also reported the possible involvement of crucial transcription factors in the process. CONCLUSIONS: Our study identified a unique meta-signature of 21 miRNAs capable of explaining pancreatic carcinogenesis and possibly holding the potential to act as biomarker for the disease detection which could be explored further.