Pancreatic adenocarcinoma (PA) is one of the most aggressive malignant tumors of the digestive tract, with a five-year survival rate of 5%. Early detection offers better possibilities of cure; however, in early stages it does not present symptoms, making the management of these patients difficult. The most commonly used biomarker for diagnosis of PA is serum CA19-9, which has a sensitivity between 70 and 80%, although, with less than 50% specificity, due to its expression in various other types of cancer. The reduced rate of apoptosis plays a crucial role in carcinogenesis, in which the cytotoxic attack and the effectiveness of pharmacological treatment are reduced. Therefore, it would be useful to associate the biomarker CA19-9 with other molecular tools to increase the accuracy of the diagnosis, such as microRNAs (miRNAs) that target apoptotic genes. The association between the expression profile of anti-apoptotic microRNAs (miRNA-15a and miRNA-16), proapoptotic microRNAs (miRNA-21, miRNA-221 and miRNA-222) and serum CA19-9 was evaluated for the diagnosis of pancreatic ductal adenocarcinoma. Twenty pancreatic tumor tissue samples, ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 19 (4): gmr18645 V.B. Filiputti et al. 2 after microdissection from patients diagnosed with pancreatic adenocarcinoma, were studied. As a control, seven samples of normal pancreas from cadaveric donors or patients undergoing pancreatic resection due to trauma were used. Serum CA19-9 was measured and the expression analysis of miRNA-21, miRNA-221, miRNA-222, miRNA-15a and miRNA-16 was measured using real-time quantitative PCR. The usefulness of pro-apoptotic and anti-apototic microRNAs alone or in association with CA19-9 in the diagnosis of PA was evaluated. The expression of miRNA-21 was significantly associated with PA, when compared with control samples. There was no significant difference in the expression of the other miRNAs. We conclude that association of CA19-9 and microRNA-21expression would increase sensitivity and accuracy in the diagnosis of PA.

IntroductionPancreatic adenocarcinoma (PA) remains one of the most aggressive malignant tumors of the digestive tract, with a five‐year survival rate of 5%. Although early detection offers the best chance to cure pancreatic adenocarcinoma, early stage disease presents little or no symptoms. The most commonly used marker for early detection of AP is serum CA19‐9, which has a sensitivity of 70% to 80%, however, with a specificity less than 50%. MiRNAs, endogenous small RNAs of approximately 17–25 nucleotides, present an altered expression in various cancers, suggesting its close relationship to disease processes, with the possibility of being a molecular biomarker for diagnosis and prognosis of cancer.ObjectivesTo evaluate the effect of the combination of the association of anti‐apoptotic microRNAs: miR‐15a and miR‐16 and pro‐apoptotic microRNAs: miR‐21, miR‐221 and miR‐222 expression profile and the protein XIAP with serum CA19‐9 in diagnosis of diagnosis of pancreatic adenocarcinoma.Patients and MethodsWe studied 23 samples of PA and 20 as control samples: 13 of normal pancreatic tissue adjacent to the tumor (PPT), collected during pancreatic resections and 7 normal pancreas (NP) from deceased donors or patients who have undergone pancreatectomy affected by trauma. CA19‐9 was measured in serum and checked for expression of the miRNAs and XIAP in PA, PPT and NP through amplification by real‐time quantitative PCR (RT‐PCR). The usefulness of miRNAs and XIAP in the diagnosis of PA, alone or associated with CA19‐9, were analyzed by the construction of ROC curves.ResultsIt was observed significant differences in the expression of miR‐21 in the comparison between the PA and NP groups (p<0.05). However, there was no significant difference in the expression of the protein XIAP between groups, as well as the expression of miR‐21 between groups NP and PPT. The combination of miR‐21 with CA19‐9 was more effective to discriminate the PA and NP (AUC‐ROC: 0.94; sensitivity: 78%, specificity: 99%) when compared with the assessments isolated.ConclusionThe expression of miR‐21 was demonstrated to be effective in discriminating between PA and NP and the association between miR‐21 and CA19‐9 increased the sensitivity and accuracy in the diagnosis of PA in the sample studied.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.