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Chronic pancreatitis is one of the main risk factors for pancreatic cancer, but it is a rare event. Inflammation and oncogenes work hand in hand as key promoters of this disease. Tobacco is another co-factor. During alcoholic chronic pancreatitis, the cumulative risk of cancer is estimated at 4% after 15 to 20 years. This cumulative risk is higher in hereditary pancreatitis: 19 and 12% in the case of PRSS1 and SPINK1 mutations, respectively, at an age of 60 years. The diagnosis is difficult due to: (i) clinical symptoms of cancer shared with those of chronic pancreatitis; (ii) the parenchymal and ductal remodeling of chronic pancreatitis rendering imaging analysis difficult; and (iii) differential diagnoses, such as pseudo-tumorous chronic pancreatitis and paraduodenal pancreatitis. Nevertheless, the occurrence of cancer during chronic pancreatitis must be suspected in the case of back pain, weight loss, unbalanced diabetes, and jaundice, despite alcohol withdrawal. Imaging must be systematically reviewed. Endoscopic ultrasound-guided fine-needle biopsy can contribute by targeting suspicious tissue areas with the help of molecular biology (search for KRAS, TP53, CDKN2A, DPC4 mutations). Short-term follow-up of patients is necessary at the clinical and paraclinical levels to try to diagnose cancer at a surgically curable stage. Pancreatic surgery is sometimes necessary if there is any doubt.

International audience; Pancreatic cancer is a public health problem because of its increasing incidence, the absence of early diagnostic tools, and its aggressiveness. Despite recent progress in chemotherapy, the 5-year survival rate remains below 5%. Liquid biopsies are of particular interest from a clinical point of view because they are non-invasive biomarkers released by primary tumours and metastases, remotely reflecting disease burden. Pilot studies have been conducted in pancreatic cancer patients evaluating the detection of circulating tumour cells, cell-free circulating tumour DNA, exosomes, and tumour-educated platelets. There is heterogeneity between the methods used to isolate circulating tumour elements as well as the targets used for their identification. Performances for the diagnosis of pancreatic cancer vary depending of the technique but also the stage of the disease: 30-50% of resectable tumours are positive and 50-100% are positive in locally advanced and/or metastatic cases. A significant prognostic value is demonstrated in 50-70% of clinical studies, irrespective of the type of liquid biopsy. Large prospective studies of homogeneous cohorts of patients are lacking. One way to improve diagnostic and prognostic performances would be to use a combined technological approach for the detection of circulating tumour cells, exosomes, and DNA.

KLF6 is ubiquitously expressed in human tissues and regulates many pathways such as differentiation, development, cellular proliferation, growth-related signal transduction, and apoptosis. We previously demonstrated that KLF6 expression is altered during liver carcinogenesis. More importantly, KLF6 invalidation results in cell cycle progression inhibition and apoptosis of liver cancer cells. On the other hand, enforced expression of KLF6 variant 2 (SV2) induces cancer cell death by apoptosis. Thus, we and others demonstrated that KLF6 and its splicing variants play a critical role in liver cancer. However, little is known on the mechanisms governing KLF6 expression in HCC. In the present work, we asked whether the 3' untranslated region (3'UTR) of the KLF6 mRNA may be responsible for regulation of KLF6 expression in HCC. We found that KLF6 mRNA stability was altered in liver-derived cell lines as compared to cervical cancer-derived cell lines and human embryonic fibroblasts. Interestingly, KLF6 mRNA was highly unstable in liver cancer-derived cell lines as compared to normal hepatocytes. We next cloned the KLF6 mRNA 3'UTR into luciferase-expressing vectors and found that gene expression and activity were strongly impaired in all liver-derived cell lines tested. In addition, we found that most the KLF6 3'UTR destabilisation activity resides between nt 1,835 and nt 2,615 of the KLF6 gene. Taken together, we provide the first steps towards better understanding of the regulation of KLF6 expression in HCC. Further work is needed to identify the factors that bind to KLF6 3'UTR to regulate its expression in liver cancer-derived cell lines.

DNA methylation is a major epigenetic modification that is strongly involved in the physiological control of genome expression. DNA methylation patterns are largely modified in cancer cells and can therefore be used to distinguish cancer cells from normal tissues. This review describes the main technologies available for the detection and the discovery of aberrantly methylated DNA patterns. It also presents the different sources of biological samples suitable for DNA methylation studies. We discuss the interest and perspectives on the use of DNA methylation measurements for cancer diagnosis through examples of methylated genes commonly documented in the literature. The discussion leads to our consideration for why DNA methylation is not commonly used in clinical practice through an examination of the main requirements that constitute a reliable biomarker. Finally, we describe the main DNA methylation inhibitors currently used in clinical trials and those that exhibit promising results.

Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer.