Serum Exosomal miRNA-1226 as Potential Biomarker of Pancreatic Ductal Adenocarcinoma

Abstract

Background Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality and it is urgent to find biomarkers for early detection of PDAC. Exosomal miRNAs are useful biomarkers for cancer detection. The aims of this study were to investigate the potential role of serum exosomal miRNA in detection of PDAC and to analyze the correlation between the levels of exosome miRNA and the tumor biological behaviors. Materials and Methods Thirteen serum samples were collected from five patients with PDACs, three healthy individuals (HIs) and five benign pancreatic lesions (BP) for a high throughput profiling analysis to identify an altered miRNA expression patterns in PDAC. Candidate exosomal miRNAs were filtered based on a second independent cohort that included 17 PDACs and 12 benign pancreatic lesions by quantitative real-time polymerase chain reaction (qRT-PCR). Four miRNAs were selected for miRNA validation as PDAC biomarkers in a subsequent set of samples. The association between candidate exosomal miRNA and tumor behavior (tumor invasion or metastases) was evaluated in 17 PDACs. In vitro studies were performed to evaluate the role of candidate exosomal miRNA on cell viability, apoptosis and cell migration in two PDAC cell lines. Results The expression of 11 miRNAs showed same trend between PDAC and BP, and between PDAC and HIs. Six of them were upregulated (miR-203b-5p, miR-342-5p, miR-337-5p, miR-149-5p, miR-877-5p, miR-203a-3p), and five were downregulated (miR-1226-3p, miR-3182, miR-625-3p, miR-624-5p, miR-664a-5p). miR-1226-3p was selected as the candidate exosomal biomarker for the PDAC detection. The expression of serum exosomal miRNA-1226-3p was downregulated in PDACs compared to the BPs (p = 0.025). miR-1226-3p had acceptable performance in predicting [area under the curve (AUC) = 0.74] PDAC. Exosomal miRNA-1226-3p level in PDAC with invasion or metastases was lower than that without invasion or metastases (p = 0.028). Transfection of miRNA-1226-3p significantly inhibited the proliferation of PANC-1 and BXP-3 cells, stimulated cell apoptosis and inhibited cell migration. Conclusion Serum exosomal miRNA-1226-3p is a potential biomarker in diagnosing and predicting the tumor invasion or metastases of PDAC.

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

“…Although multiple studies are trying to find effective diagnostic markers for Pca, early diagnosis of Pca is still difficult ( 25 ). Several circulating exosomal miRNA biomarkers have been reported for the diagnosis of Pca 19 , including miR-1226 ( 26 ), miR-196a/1246 ( 27 ), miR-191/21/451a ( 28 ), and miR-10b/21/30c/161a/let-7a ( 29 ). However, few studies have investigated the diagnostic value of Exo-miR-19b ( 20 ), and no reports have been performed in Pca.…”

Identification of Circulating Exosomal miR-101 and miR-125b Panel Act as a Potential Biomarker for Hepatocellular Carcinoma

“…Yokota and colleagues reported that serum exosomal miR-638 is a prognostic marker of HCC via downregulation of endothelial cell VE-cadherin and ZO-1 [ 15 ]. Moreover, Wang and colleagues suggested that serum exosomal miRNA-1226-3p is a potential biomarker for diagnosing and predicting the tumor invasion or metastases of pancreatic ductal adenocarcinoma [ 16 ]. Furthermore, Shen and colleagues demonstrated that cancer-derived exosomal miR-7641 may serve as a promising noninvasive diagnostic biomarker and potential targetable candidate in breast cancer treatment [ 20 ].…”

“…Exosomes are remarkably stable in body fluids, and they can carry various contents from donor cells to recipient cells, including proteins, lipids, DNA, and RNA [ 13 , 14 ]. Emerging evidence has demonstrated that exosomes and their delivered miRNAs have potential use as novel potential biomarkers in various cancers, such as HCC [ 15 ], pancreatic ductal adenocarcinoma [ 16 ], glioblastoma [ 17 ], prostate cancer [ 18 ], colorectal cancer [ 19 ], and breast cancer [ 20 ]. However, many circulating miRNAs that have been identified as potential diagnostic biomarkers of HCC were not selected through high-throughput screening; thus, other miRNAs that may have a higher diagnostic value were ignored.…”

MiR-149-5p: An Important miRNA Regulated by Competing Endogenous RNAs in Diverse Human Cancers

“…In addition to GC, HCC and CRC, miR-149-5p has also been studied in other digestive system cancers, including oral cancer, esophageal cancer and ductal adenocarcinoma of the pancreas (70)(71)(72)(73)(74)(75)(76).…”

“…Compared with healthy people and patients with benign pancreatic lesions, the expression of miR-149-5p in serum exosome of patients with pancreatic ductal adenocarcinoma (PDAC) was up-regulated (74). But no further studies elucidated the role of miR-149-5p in PDAC, thus to explore the prognostic and diagnostic role of miR-149-5p, more researches should focus on its function in tumor initiation and progression rather than merely examining its expression level.…”