Circulating microRNA-99 family as liquid biopsy marker in pancreatic adenocarcinoma

purposerecently, we identified the microrna-99 family as unfavorable prognostic factor in patients with pancreatic ductal adenocarcinoma (pdac). the aim of this study is to evaluate its value as circulating biomarker for pdac. methods:tissue and corresponding preoperative blood samples of 181 patients with pdac uicc stages i–iv (n = 90), intraductal papillary mucinous neoplasm (ipmn, n = 11), chronic pancreatitis (n = 40), pancreatic cystadenoma (n = 20), and age-matched healthy blood serum controls (n = 20) were collected between 2014 and 2017 prospectively. expression of microrna-21 as confirmatory marker and the microrna-99 family, consisting of microrna-99a, -99b, and -100, was analyzed by qrt-pcr. target analysis of insulin-like growth factor 1 receptor (igf1r) was performed using tissue array immunohistochemistry and western blotting. results:expression of microrna-99 family members was significantly increased in macrodissected tumor tissue and corresponding blood serum samples (p < 0.05) of patients with pdac of all stages. correspondingly, its target protein igf1r was upregulated (p < 0.001) in carcinoma tissue. circulating and tissue-related microrna-100 could well discriminate pdac from healthy samples with area under the receiver operating characteristic (roc) curve (auc) values of 0.81 and 0.85, respectively. low expression of circulating microrna-100 was associated with significantly improved overall survival (p = 0.004) and recurrence-free survival (p = 0.03) in multivariate analyses. circulating microrna-21 was overexpressed in pdac with fair discrimination between pdac and healthy controls (auc = 0.71) and decreased overall survival (p = 0.046) and recurrence-free survival (p = 0.03) in pdac patients. conclusion:smultivariate survival and roc analyses identified circulating microrna-100 as potential diagnostic and prognostic marker in pdac patients.