Introduction

Pancreatic cancer is a fast progressive and highly aggressive malignancy.Clinically，pancreatic cancer exhibits profound resistance to existing treatment modalities and surgical resection remains the only chance for cure of pancreatic cancer patients（Vincent et al.2011）.Development of efficient early detection modality is of highest priority.Epidemiological studies have shown that chronic pancreatitis is one of the major risk factors for pancreatic cancer，and patients with chronic pancreatitis have 2.3 to 18.5-fold increased risk than normal controls（Malka et al.2002）.Delineating the progression from chronic pancreatitis to pancreatic cancer and identifying the genetic and epigenetic events in this process will help detect early-stage pancreatic cancer in chronic pancreatitis cases and improve prognosis of these patients.

Hereditary pancreatitis represents the best model to dissect the causal linkage between chronic pancreatitis and pancreatic cancer.Epidemiological analysis has shown that hereditary pancreatitis ranks the strongest known risk factor for pancreatic cancer（Schneider and Whitcomb 2002）.With the advent of molecular techniques，several germ-line mutations within certain genes，e.g.，PRSS1 and CFTR，are identified as the major cause for hereditary pancreatitis（Keiles and Kammesheidt 2006）.However，these mutations are rarely detected in common chronic pancreatitis cases，indicating that these genes are not directly associated with development of pancreatic cancer（Hengstler et al.2000；Malats et al.2001）.It is widely believed that inflammation itself，but not those hereditary genes，promotes pancreatic cancer development and progression（Lu et al.2006）.(https://www.daowen.com)

Once inflammation is initiated，inflammatory cells，especially macrophages，are recruited to the inflicted sites and release cytokines，growth factors，matrix-degrading enzymes and others（Jackson and Evers 2006）.All those inflammatory factors，in combination with macrophages，constitute the extrinsic signals，which reprogram the microenvironment to facilitate pancreatic cancer development and progression（Jackson and Evers 2006）.Evidently，the inflammatory milieu may disable surveillance mechanisms and destabilize the genome in normal pancreatic cells，which will enhance the generation and accumulation of genetic events within these cells and accelerate the process of pancreatic tumor formation.Mechanistically，a number of dysregulated signaling pathways are commonly identified in both chronic pancreatitis and pancreatic cancer tissues.Of clinical significance，most of those altered pathways，including cytokines，NF-κB，reactive oxygen species，PPARy，and so on，have potential value in pancreatic cancer treatment（Uomo et al.2010）.

However，chronic pancreatitis and pancreatic cancer are two entirely different diseases with distinct prognosis.Under certain circumstances，it is clinically difficult to distinguish from each other（Sakorafas and Tsiotou 1999）.Given that numerous signaling pathways are similarly altered in both chronic pancreatitis and pancreatic cancer；it is a daunting challenge to identify potential biomarkers for the differential diagnosis of the two diseases.Currently，all the global proteomic studies have failed to identify pancreatic cancer specific biomarkers，which may arguably be due to the low abundance of those biomarkers in human tissues.Nonetheless，recent studies have discovered a list of protein markers，a combination of which may enhance the diagnostic efficacy for pancreatic cancer（Chan et al.2014）.Moreover，the stability and abundance of DNA and microRNAs in human tissues have also been explored for their clinical utility as pancreatic cancer biomarkers（Schultz et al.2014）.