Therapy for pancreatic ductal adenocarcinoma remains challenging, and the chances of a complete cure are very limited. As in other types of cancer, the expression and role of miRNAs in controlling the biological properties of this type of tumor have been extensively studied. A better insight into miRNA biology seems critical to refining diagnostics and improving their therapeutic potential. In this study, we focused on the expression of miR-21, -96, -196a, -210, and -217 in normal fibroblasts, cancer-associated fibroblasts prepared from a ductal adenocarcinoma of the pancreas, and pancreatic carcinoma cell lines. We compared these data with miRNAs in homogenates of paraffin-embedded sections from normal pancreatic tissues. In cancer-associated fibroblasts and cancer cell lines, miRNAs differed significantly from the normal tissue. In detail, miR-21 and -210 were significantly upregulated, while miR-217 was downregulated. Similar transcription profiles were earlier reported in cancer-associated fibroblasts exposed to hypoxia. However, the cells in our study were cultured under normoxic conditions. We also noted a relation to IL-6 production. In conclusion, cultured cancer-associated fibroblasts and carcinoma cells reflect miR-21 and -210 expression similarly to the cancer tissue samples harvested from the patients.

• Klíčová slova
• IL-6, cancer-associated fibroblast, hypoxia, miR-21, miR-210, miRNA, pancreas,
• MeSH
• diabetes mellitus MeSH
• duktální karcinom pankreatu * patologie   MeSH
• faciální stigmatizace MeSH
• fibroblasty asociované s nádorem * metabolismus   MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• mozeček abnormality   MeSH
• nádorové buněčné linie MeSH
• nádory slinivky břišní * patologie   MeSH
• regulace genové exprese u nádorů MeSH
• růstová retardace plodu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mikro RNA * MeSH
• MIRN217 microRNA, human MeSH Prohlížeč

We compare two types of pancreatic carcinoma samples obtained by EUS-guided fine needle biopsy (EUS-FNB) in terms of the success rates and clinical validity of analysis of two most commonly investigated DNA/RNA pancreatic cancer markers, KRAS mutations and miR-21 expression. 118 patients with pancreatic ductal adenocarcinoma underwent EUS-FNB. The collected sample was divided, one part was stored in a stabilizing solution as native aspirate (EUS-FNA) and second part was processed into the cytological smear (EUS-FNC). DNA/RNA extraction was followed by analysis of KRAS mutations and miR-21 expression. For both sample types, the yields of DNA/RNA extraction and success rates of KRAS mutation and miRNA expression were evaluated. Finally, the resulting KRAS mutation frequency and miR-21 prognostic role were compared to literature data from tissue resections. The overall amount of isolated DNA/RNA from EUS-FNC was lower compared to the EUS-FNA, average yield 10 ng vs 147 ng for DNA and average yield 164 vs. 642 ng for RNA, but the success rates for KRAS and miR-21 analysis was 100% for both sample types. The KRAS-mutant detection frequency in EUS-FNC was 12% higher than in EUS-FNA (90 vs 78%). The prognostic role of miR-21 was confirmed in EUS-FNC (p = 0.02), but did not reach statistical significance in EUS-FNA (p = 0.06). Although both types of EUS-FNB samples are suitable for DNA/RNA extraction and subsequent DNA mutation and miRNA expression analysis, reliable results with clinical validity were only obtained for EUS-FNC.

• Klíčová slova
• EUS-FNA, KRAS, Pancreatic cancer, miR-21,
• MeSH
• biopsie tenkou jehlou pod endosonografickou kontrolou MeSH
• cytodiagnostika metody   MeSH
• DNA analýza   MeSH
• duktální karcinom pankreatu diagnóza   MeSH
• fixace tkání metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA analýza   MeSH
• mutace MeSH
• nádorové biomarkery analýza   MeSH
• nádory slinivky břišní diagnóza   MeSH
• odběr biologického vzorku metody   MeSH
• protoonkogenní proteiny p21(ras) genetika   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• DNA MeSH
• KRAS protein, human MeSH Prohlížeč
• mikro RNA MeSH
• MIRN21 microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protoonkogenní proteiny p21(ras) MeSH

Evidence on equilibrative nucleoside transporter 1 (ENT1) and microRNA-21 (miR‑21) is not yet sufficiently convincing to consider them as prognostic biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the prognostic value of ENT1/ENT1, miR-21, and neurogenic locus homolog protein 3 gene (NOTCH3) in a well-defined cohort of resected patients treated with adjuvant gemcitabine chemotherapy (n = 69). Using a combination of gene expression quantification in microdissected tissue, immunohistochemistry, and univariate/multivariate statistical analyses we did not confirm association of ENT1/ENT1 and NOTCH3 with improved disease-specific survival (DSS). Low miR-21 was associated with longer DSS in patients with negative regional lymph nodes or primary tumor at stage 1 and 2. In addition, downregulation of ENT1 was observed in PDAC of patients with high ENT1 expression in normal pancreas, whereas NOTCH3 was upregulated in PDAC of patients with low NOTCH3 levels in normal pancreas. Tumor miR‑21 was upregulated irrespective of its expression in normal pancreas. Our data confirmed that patient stratification based on expression of ENT1/ENT1 or miR‑21 is not ready to be implemented into clinical decision-making processes. We also conclude that occurrence of ENT1 and NOTCH3 deregulation in PDAC is dependent on their expression in normal pancreas.

• Klíčová slova
• adjuvant gemcitabine monotherapy, equilibrative nucleoside transporter 1, miR-21, neurogenic locus homolog protein 3, prognostic biomarker, resected pancreatic ductal adenocarcinoma,
• Publikační typ
• časopisecké články MeSH

Blood plasma microRNAs (miRNAs) are emerging as a clinically useful tool for non-invasive detection and prognosis estimation in various cancer types including pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to provide an independent validation of circulating miRNAs identified in previous studies as diagnostic and/or prognostic biomarkers in PDAC. Based on the literature search, 6 miRNAs were chosen as candidates for independent validation; miR-21-5p, miR-375, miR-155, miR-17-5p, miR-126-5p and miR-1290. Validation of these miRNAs was performed in a cohort of 25 patients with PDAC undergoing surgical resection and 24 healthy donors. Plasma levels of miRNAs were determined using quantitative real-time PCR. We confirmed significantly higher levels of all tested miRNA in blood plasma of PDAC patients in comparison to healthy controls with miR-21-5p showing the highest analytical performance (p<0.001; AUC>0.99). Increased levels of miR-21-5p (p=0.045) and miR-375 (p=0.013) were significantly associated with overall survival. Multivariate analysis demonstrated that miR-21-5p is a significant unfavorable prognostic factor independent on other clinical variables including adjuvant chemotherapy (hazard ratio 2.95; 95% CI 1.06-8.18; p=0.038). Our preliminary data indicate promising diagnostic and prognostic utility of plasma miR-21-5p in PDAC patients.

• Klíčová slova
• Pancreatic ductal adenocarcinoma, diagnosis, miR-21-5p, microRNAs, plasma, prognosis,
• MeSH
• adenokarcinom krev   patologie   chirurgie   MeSH
• duktální karcinom pankreatu krev   patologie   chirurgie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA krev   MeSH
• míra přežití MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory slinivky břišní krev   patologie   chirurgie   MeSH
• následné studie MeSH
• předoperační péče * MeSH
• prognóza MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mikro RNA MeSH
• MIRN21 microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies with increasing incidence. The poor prognosis is due to the aggressive nature of the tumor, late detection, and the resistance to chemotherapy and radiotherapy. A radical surgery procedure is the only treatment that has been shown to improve the 5-year survival rate to 20-25%. However, the majority of patients (80-85%) are diagnosed with locally advanced or metastatic disease and just 15-20% patients are diagnosed in an early stage allowing them to undergo the potentially curative surgical resection. The early detection of PDAC without the use of invasive methods is challenging and discovery of a cost-effective biomarker with high specificity and sensitivity could significantly improve the treatment and survival in these patients. In this review, we summarize current and newly examined biomarkers in early PDAC detection.

• MeSH
• analýza přežití MeSH
• časná detekce nádoru metody   MeSH
• dospělí MeSH
• duktální karcinom pankreatu krev   diagnóza   mortalita   chirurgie   MeSH
• hodnocení rizik MeSH
• invazivní růst nádoru patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery krev   MeSH
• nádory slinivky břišní krev   diagnóza   mortalita   chirurgie   MeSH
• pankreatektomie metody   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• prognóza MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• nádorové biomarkery MeSH