Mitochondrial DNA and MitomiR Variations in Pancreatic Cancer: Potential Diagnostic and Prognostic Biomarkers

Pancreatic cancer is an aggressive disease with poor prognosis. Only about 15-20% of patients diagnosed with pancreatic cancer can undergo surgical resection, while the remaining 80% are diagnosed with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). In these cases, chemotherapy and radiotherapy only confer marginal survival benefit. Recent progress has been made in understanding the pathobiology of pancreatic cancer, with a particular effort in discovering new diagnostic and prognostic biomarkers, novel therapeutic targets, and biomarkers that can predict response to chemo- and/or radiotherapy. Mitochondria have become a focus in pancreatic cancer research due to their roles as powerhouses of the cell, important subcellular biosynthetic factories, and crucial determinants of cell survival and response to chemotherapy. Changes in the mitochondrial genome (mtDNA) have been implicated in chemoresistance and metastatic progression in some cancer types. There is also growing evidence that changes in microRNAs that regulate the expression of mtDNA-encoded mitochondrial proteins (mitomiRs) or nuclear-encoded mitochondrial proteins (mitochondria-related miRs) could serve as diagnostic and prognostic cancer biomarkers. This review discusses the current knowledge on the clinical significance of changes of mtDNA, mitomiRs, and mitochondria-related miRs in pancreatic cancer and their potential role as predictors of cancer risk, as diagnostic and prognostic biomarkers, and as molecular targets for personalized cancer therapy.