Combination of microRNA-21 expression with theserum marker CA19-9 increases the accuracy ofdiagnosis of pancreatic adenocarcinoma

摘要

Pancreatic adenocarcinoma (PA) is one of the mostaggressive malignant tumors of the digestive tract, with a five-yearsurvival rate of 5%. Early detection offers better possibilities of cure;however, in early stages it does not present symptoms, making themanagement of these patients difficult. The most commonly usedbiomarker for diagnosis of PA is serum CA19-9, which has asensitivity between 70 and 80%, although, with less than 50%specificity, due to its expression in various other types of cancer. Thereduced rate of apoptosis plays a crucial role in carcinogenesis, inwhich the cytotoxic attack and the effectiveness of pharmacologicaltreatment are reduced. Therefore, it would be useful to associate thebiomarker CA19-9 with other molecular tools to increase theaccuracy of the diagnosis, such as microRNAs (miRNAs) that targetapoptotic genes. The association between the expression profile ofanti-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 pancreaticductal adenocarcinoma. Twenty pancreatic tumor tissue samples, after microdissection from patients diagnosed with pancreaticadenocarcinoma, were studied. As a control, seven samples of normalpancreas from cadaveric donors or patients undergoing pancreaticresection due to trauma were used. Serum CA19-9 was measured andthe expression analysis of miRNA-21, miRNA-221, miRNA-222,miRNA-15a and miRNA-16 was measured using real-timequantitative PCR. The usefulness of pro-apoptotic and anti-apototicmicroRNAs alone or in association with CA19-9 in the diagnosis ofPA was evaluated. The expression of miRNA-21 was significantlyassociated with PA, when compared with control samples. There wasno significant difference in the expression of the other miRNAs. Weconclude that association of CA19-9 and microRNA-21expressionwould increase sensitivity and accuracy in the diagnosis of PA.