Plasma-Derived Exosome MiR-19b Acts as a Diagnostic Marker for Pancreatic Cancer

Abstract

BackgroundDiagnosis of pancreatic cancer (Pca) is challenging. This study investigated the value of plasma-derived exosome miR-19b (Exo-miR-19b) in diagnosing patients with Pca.MethodsPlasma was collected from 62 patients with Pca, 30 patients with other pancreatic tumor (OPT), 23 patients with chronic pancreatitis (CP), and 53 healthy volunteers. MiR-19b levels in plasma-derived exosomes were detected.ResultsPlasma-derived Exo-miR-19b levels normalized using miR-1228 were significantly lower in Pca patients than in patients with OPT, CP patients, and healthy volunteers. The diagnostic values of Exo-miR-19b normalized using miR-1228 were superior to those of serum cancer antigen 19-9 (CA19-9) in differentiating Pca patients from healthy volunteers (area under the curve (AUC): 0.942 vs. 0.813, p = 0.0054), potentially better than those of CA19-9 in differentiating Pca patients from CP patients (AUC: 0.898 vs. 0.792, p = 0.0720), and equivalent to those of CA19-9 in differentiating Pca patients from patients with OPT (AUC: 0.810 vs. 0.793, p = 0.8206). When normalized using Caenorhabditis elegans miR-39 (cel-miR-39), Exo-miR-19b levels in Pca patients were significantly higher than those in patients with OPT, CP patients, and healthy volunteers. The diagnostic values of Exo-miR-19b normalized using cel-miR-39 were equivalent to those of CA19-9 in differentiating Pca patients from healthy volunteers (AUC: 0.781 vs. 0.813, p = 0.6118) and CP patients (AUC: 0.672 vs. 0.792, p = 0.1235), while they were inferior to those of CA19-9 in differentiating Pca patients from patients with OPT (AUC: 0.631 vs. 0.793, p = 0.0353).ConclusionPlasma-derived Exo-miR-19b is a promising diagnostic marker for Pca. The diagnostic value of plasma-derived Exo-miR-19b normalized using miR-1228 is superior to that of serum CA19-9 in differentiating patients with Pca from healthy volunteers.

Plasma Exosome-Derived microRNAs as Potential Diagnostic and Prognostic Biomarkers in Brazilian Pancreatic Cancer Patients

“…In addition, the authors observed that miR-21 could distinguish patients at the early stage of the disease from healthy controls and from advanced-stage patients [ 53 ]. With the same research bias context, it has been reported that the levels of plasma exosome-derived miR-19b, normalized using miR-1228, were significantly lower in pancreatic cancer patients than in healthy volunteers [ 54 ]. Its diagnostic value was superior to that of serum CA19-9 [ 54 ], but reports have also shown that miR-19b is significantly overexpressed in the serum from pancreatic cancer patients [ 49 ].…”

Extracellular vesicle biomarkers for pancreatic cancer diagnosis: a systematic review and meta-analysis

“…Across 39 included studies, which involved 2037 PC cases and 1632 noncancerous, 24 studies were conducted in Asia [ 25 , 44 , 53 , 60 – 64 , 67 – 72 , 74 , 76 – 80 , 82 – 85 ], eight were in Europe [ 24 , 30 , 31 , 43 , 59 , 73 , 75 , 81 ], and seven were in North America [ 33 , 34 , 45 – 47 , 58 , 86 ]. Sample size of PC cases varied from 6 to 284 (median number, 33) and of noncancerous groups varied from 6 to 152 (median number, 29), respectively.…”

“…The detail information of mean age, sex distribution, number of cases and controls, detection approaches, and PC stage in included studies were all described in Tables 1 , 2 and 3 . Seventeen studies focused on the diagnostic performance of individual EV RNAs (microRNAs in nine studies [ 25 , 31 , 45 , 46 , 59 , 61 , 62 , 64 , 68 , 70 , 72 , 74 , 78 , 84 ], messenger RNAs in two studies [ 44 , 53 ], small nucleolar RNAs in one study [ 53 ], and long noncoding RNAs in one study [ 80 ]), one of which was validated by blind external test [ 44 ], shown in Table 1 ; Sixteen focused on individual EV proteins (Membrane proteins (MP) in thirteen studies [ 24 , 30 , 33 , 34 , 47 , 58 , 60 , 62 , 75 , 76 , 79 , 82 , 83 ], non-membrane proteins (nMPs) in six studies [ 47 , 58 , 67 , 69 , 81 , 82 ]), three of which were applied independent validation tests [ 30 , 34 , 47 ]. One study reported 446 individual EV proteins with AUC value greater than 0.7 and we selected 156 EV proteins with p value less than 0.01 for analysis [ 58 ], shown in Table 2 .…”

“…The isolation and detection methods of EVs were diversity, 15 studies used the commercial kits [ 24 , 25 , 46 , 53 , 60 , 61 , 64 , 68 , 70 – 72 , 74 , 83 – 85 ], 11 studies used ultracentrifugation [ 31 , 43 , 45 , 58 , 59 , 63 , 69 , 73 , 75 , 79 , 81 ], one study was not stated the isolation and detection method of EV [ 80 ], the remaining studies developed new isolation and detection techniques including ephrin type-A receptor 2/nanoplasmon-enhanced scattering (EphA2-EV-nPES assay) [ 34 ], PDA encapsulated antibody-reporter-Ag(shell)-Au(core) multilayer, surface-Enhanced Raman Scattering (chip-exosome-PEARL SERS immunosensor) [ 82 ], AC electrokinetic integrated biomarker assay [ 86 ], nanoplasmonic sensor assay (NPS chip) [ 47 ], lipid-polymer hybrid nanoparticle/catalyzed hairpin DNA circuit (LPHN-CHDC biochip) [ 44 ], immunogold transmission electron microscopy [ 30 ], Sequential size-exclusion chromatography (SSEC) [ 67 ], antibody-conjugated magnetic beads, bivalent cholesterol-modified RNA − DNA duplexes (AbMB-bioChol) platform [ 76 ], nanoparticle-and dyebased fluorescent immunoassay [ 33 ], immuno-capture using magnetic beads [ 77 ], and 3D microfluidic chip [ 62 , 78 ] (Additional file 1 ).…”

“…Among them, miR-21 and miR-10b were the highest frequently reported RNA which was reported in 6 times. The expression direction of most EV miRNAs were up-regulate, apart from miR-122 [ 45 ], miR-let7 [ 45 ], miR-1226-3p [ 64 ], miR-19b-3p [ 72 ], miR-3158-3p [ 78 ], miR-4732-3p [ 78 ], miR-7706 [ 78 ], and miR-486-3p [ 78 ] were down-regulate (Additional file 2 ). The expression directions of miR-192-5p [ 59 ] and miR-196b [ 46 ] were not reported (Additional file 2 ).…”