Combination of plasma microRNAs with serum CA19‐9 for early detection of pancreatic cancer

Abstract

This study was performed to identify plasma microRNAs (miRNAs) as diagnostic biomarkers for pancreatic cancer (PCa) and to assess their supplementary role with serum CA19-9 in early identification of tumors. Plasma RNAs were extracted from 140 PCa patients, 111 chronic pancreatitis (CP) patients and 68 normal controls, and the relative abundances of seven miRNAs (miR-16, 21, 155, 181a, 181b, 196a and 210) were measured using real-time PCR. Their diagnostic utility for PCa and correlation with clinical characteristics were analyzed. All seven miRNAs were significantly aberrantly upregulated in the PCa group compared with both the CP and normal groups, between which only four miRNAs (miR-155, 181a, 181b and 196a) were significantly different. Logistic modeling proved that only miR-16 and miR-196a possessed an independent role in discriminating PCa from normal and CP. Furthermore, after including serum CA19-9 in the logistic model, the combination of miR-16, miR-196a and CA19-9 was more effective for discriminating PCa from non-PCa (normal1CP) (AUC-ROC, 0.979; sensitivity, 92.0%; specificity, 95.6%), and for discriminating PCa from CP (AUC-ROC, 0.956; sensitivity, 88.4%; specificity, 96.3%) compared with the miRNA panel (miR-161miR-196a) or CA19-9 alone. Most significantly, the combination was effective at identification of tumors in Stage 1 (85.2%). In conclusion, plasma miRNAs were effective for distinguishing PCa from non-PCa (normal1CP). The combination of miR-16, miR-196a and CA19-9 was more effective for PCa diagnosis, especially in early tumor screening.

Circulating microRNAs as diagnostic biomarkers for pancreatic cancer

“…Some studies have also combined circulating miRNA expression levels with CA 19-9 to improve diagnostic accuracy. [9,14,15] However, the diagnostic combination of miR-486-5p and miR-938 with CA 19-9 was not performed in this study.…”

“…Small nuclear U6 is less stable in fluids than in tissues, [7] whilst miR-16 is a red blood cell expressed miRNA, and variations in blood cell count and/or any hemolysis could have important implications. [19] Interestingly, highly expressed circulating miR-16 [14] and peripheral blood mononuclear cell miR-16 [15] levels have themselves been shown to discriminate PDAC from HC, and those with benign disease. Therefore, the combined use of snU6 and miR-16 might not be appropriate as endogenous control, whereas a miRNA with the least change in expression across the various samples in the array could have been chosen as a normalizer.…”

Increased plasma microRNA and CD133/CK18-positive cancer cells in the pleural fluid of a pancreatic cancer patient with liver and pleural metastases and correlation with chemoresistance

“…A total of 2.5 µl synthetic C. elegans miRNA, cel-miR-39 (2x10 -3 pmol/µl synthetic RNA oligonucleotides; Qiagen, Hilden, Germany), was applied to each sample as an internal control. The method used for the identification of miR-16, miR-21, miR-103 and miR-151 in the plasma was described previously (5). The relative abundance of the miRNAs was determined using the following equation: Relative miRNA abundance = -∆∆Ct = -[(Sample Ct target -Sample Ct cell-miR-39 ) -(Control Ct target -Control Ct cell-miR-39 )].…”

“…Downregulation of miR-21 results in an increased sensitivity of these cells to gemcitabine (3,(12)(13)(14). Measurement of plasma miR-21 levels and serum CA19-9 may be helpful for early detection of pancreatic cancer (5).…”

Pancreatic Cancer in Chronic Pancreatitis

“…Liu et al [34] reported a sensitivity of 88.4 % and specificity of 96.3 % in differentiating PC from CP using a combination of micro-RNA and CA 19-9.…”