Plasma exosome miR-196a and miR-1246 are potential indicators of localized pancreatic cancer

Abstract

Patients with localized pancreatic cancer (stage I and stage IIA) have a much higher survival rate than those presenting at later stages, yet early detection remains a challenge to this malignancy. The aim of this study was to evaluate whether exosome miRNA signatures are indicative of localized pancreatic cancer. Exosomes were collected from the conditioned media of pancreatic cancer cell lines and plasma samples of localized pancreatic cancer patients (Stage I-IIA, n=15), and healthy subjects (n=15). Cellular and exosome miRNAs from pancreatic cancer cell lines were profiled by next-generation small RNA sequencing. Plasma exosome miRNA expression was analyzed by qRT-PCR. We found that certain miRNAs, such as miR-196a and miR-1246, are highly enriched in pancreatic cancer exosomes. Consistently, plasma exosome miR-196a and miR-1246 levels were significantly elevated in pancreatic cancer patients as compared to healthy subjects. An analysis of the cancer subtypes indicated that plasma exosome miR-196a is a better indicator of pancreatic ductal adenocarcinoma (PDAC), whereas plasma exosome miR-1246 is significantly elevated in patients with intraductal papillary mucinous neoplasms (IPMN). In contrast, there were no differences in the plasma exosome miR-196a and miR-1246 levels between patients with pancreatic neuroendocrine tumors (NET) and healthy subjects. In conclusion, we demonstrate that certain miRNA species, such as miR-196a and miR-1246, are highly enriched in pancreatic cancer exosomes and elevated in plasma exosomes of patients with localized pancreatic cancer.

Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

“…Compared with normal tissues, miR-143 was up-regulated in both PDAC and PVAC tumor samples, which may reflect the histological features and biological behavior of different PCs [44]. Accumulating evidence indicates that the serum miR-196a expression level is able to predict the median survival time of PDAC patients [45,46]. The OS analysis of the up-regulated DEmiRNAs was consistent with the results of the present study.…”

Pancreatic cancer cell–derived exosomal microRNA‐27a promotes angiogenesis of human microvascular endothelial cells in pancreatic cancer via BTG2

“…The co‐culture of exosomes and HMVEC has been found to induce endothelial dysfunction in patients suffering from acute chest syndrome . Exosomes secreted by cancer cells are widely known with the ability to enter the tumour circulation and microenvironment, highlighting the potential of exosomal miRs as promising biomarkers capable of facilitating the improvement of cancer detection . The aberrant expression of exosomal miR‐21 has been detected in PC, which may serve as an early diagnostic marker for PC .…”

Circulating microRNA‐1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma

“…In addition to these findings, other results for cancer‐derived exosomes reinforce the argument that miR‐1246 is involved in tumor progression and metastasis, and has been proposed to serve as a biomarker for certain malignancies. Many reports have shown close associations between overexpression of circulating miR‐1246 and prognosis in several types of cancer, including non‐small‐cell lung prostate, colon, breast, pancreas, cervix, oral, and esophageal carcinomas …”