miR-125 is a Novel Biomarker in Pancreatic Cancer Patients

Approximately 46,420 Americans are diagnosed with pancreatic cancer and 39,590 individuals die from the disease annually. Pancreatic cancer is associated with a less than 5% five-year survival rate.1 Early diagnosis is rare and surgical treatment is most beneficial before the cancer becomes locally invasive or metastatic. Previously, we identified in vitro DAMPmiRs (Damage Associated Molecular Pattern molecule induced microRNAs, miR-34c and miR-214) that are differentially expressed in peripheral blood mononuclear cells (PBMCs) upon DAMP stimulation and play an important role in regulating the inflammatory response via targeting inflammatory pathways. DAMPs are passively released into the local micro-environment, and progressively, into the systemic circulation to initiate early innate and adaptive immune responses.2,3 Whether the microRNA (miRNA) expression in pancreatic cancer patients’ PBMC is different from those of normal healthy individuals is unknown. Here, we examined the miRNA expression profile of age and sex matched samples to identify potential miRNA markers. One of the most promising markers (miR-125a-5p) was selected for further analysis in patients enrolled in our recently completed phase I/II pre-operative treatment with hydroxychloroquine and gemcitabine. We also evaluated how individual immunological stimuli affect miR-125a-5p expression in normal PBMC and validated several miR-125a-5p predicted down-stream targets