Circulating microRNAs as diagnostic biomarkers for pancreatic cancer

Large, Tessa Y.S. Le; Meijer, Laura L.; Prado, Mireia Mato; Kazemier, Geert; Frampton, Adam E.; Giovannetti, Elisa

doi:10.1586/14737159.2015.1112273

Cited by 27 publications

(19 citation statements)

References 34 publications

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“…In addition, miR-221 has been proposed as a useful biomarker for predicting malignant outcomes [85], while miR-486-5p and miR-938 seem to discriminate PDAC patients from healthy controls and those with chronic pancreatitis. Remarkably, the diagnostic ability of miR-486-5p was comparable to that of CA19-9, which stands for the most reliable diagnostic serum marker [86]. Recently, Goggin's group demonstrated that miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls [87].…”

Section: Review Vorvis Koutsioumpa and Iliopoulos Future Science Groupmentioning

confidence: 97%

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

2016

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Pancreatic cancer is a devastating malignancy that ranks as the fourth leading cause of cancerrelated deaths worldwide. Dismal prognosis is mainly attributable to limited knowledge of the molecular pathogenesis of the disease. miRNAs have been found to be deregulated in pancreatic cancer, affecting several steps of initiation and aggressiveness of the disease by regulating important signaling pathways, such as the KRAS and Notch pathways. Moreover, the effect of miRNAs on regulating cell cycle events and expression of transcription factors has gained a lot of attention. Recent studies have highlighted the application of miRNAs as biomarkers and therapeutic tools. The current review focuses on latest advances with respect to the roles of miRNAs in pancreatic ductal adenocarcinoma associated signaling pathways and miRNA-based therapeutics. KEYWORDS• antisense oligonucleotides • miRNAs • pancreatic cancer Pancreatic cancer overview Pancreatic ductal adenocarcinoma (PDAC) is the predominant form of pancreatic neoplasms and accounts for greater than 85% of the clinical cases [1]. The disease develops via acinar-ductal metaplasia and neoplastic precursor lesions [2]. In the USA alone, 48,960 new cases of pancreatic cancer were expected to occur in 2015, with an estimated 40,560 deaths, about the same number in women (19,850) as in men (20,710). Over 96% are cancers arising from exocrine pancreas. Endocrine carcinomas are often diagnosed at a younger age and exhibit a better prognosis. From 2007 to 2011, mortality rates increased slightly by 0.3% per year. For all stages combined, the 1-and 5-year relative survival rates are 28 and 7%, respectively. For the small percentage of people diagnosed with local disease (9%), the 5-year survival is 26%, while more than half of patients (53%) are diagnosed at a late stage for which 1-and 5-year survival rates reach 15 and 2%, respectively [3]. These numbers are a staggering example of the poor prognosis associated with PDAC.While new therapeutic options are emerging for nonhematologic malignancies, molecular-targeted therapies for pancreatic cancer have failed to make any positive impact on patient survival. In 1993, the Nobel Prize-winning discovery of small interference RNAs (siRNAs) led to an outburst of knowledge on RNA interference and gene regulation [4]. Since then, thousands of research studies have described the functional role of small noncoding RNAs, named miRNAs, in a vast panel of human pathologies. In 2002, a small genomic region in chromosome 13q14 comprising miR-15a and miR-16-1 genes was found to be commonly deleted in chronic lymphocytic leukemia, For reprint orders, please contact: reprints@futuremedicine.com

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Section: Review Vorvis Koutsioumpa and Iliopoulos Future Science Groupmentioning

confidence: 97%

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

2016

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“…Recently, one hypothesis has clearly demonstrated that cancer cells contribute to the pool of circulating miRNAs, which allows for the detection of cancer-specific miRNAs in a patient’s circulation. Circulating miRNAs represent a rich resource of potential biomarkers for PC diagnosis 21, 22 . In the present study, we used a two-phase design to investigate the diagnostic accuracies of circulating miRNAs in patients with PC.…”

Section: Introductionmentioning

confidence: 99%

Circulating miRNA-21-5p as a diagnostic biomarker for pancreatic cancer: evidence from comprehensive miRNA expression profiling analysis and clinical validation

Zhang

Lin

et al. 2017

Sci Rep

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Pancreatic cancer (PC) is a highly fatal disease worldwide and is often misdiagnosed in its early stages. The exploration of novel non-invasive biomarkers will definitely benefit PC patients. Recently, circulating miRNAs in body fluids are emerging as non-invasive biomarkers for PC diagnosis. In this study, we first conducted comprehensive robust rank aggregation (RRA) analysis based on 21 published miRome profiling studies. We statistically identified and clinically validated a miRNA expression pattern in PC patients. These miRNAs consisted of four up-regulated (hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-210-3p and hsa-miR-155-5p) and three down-regulated miRNAs (hsa-miR-217, hsa-miR-148a-3p and hsa-miR-375). Among them, hsa-miR-21-5p was one of the most highly expressed miRNAs in the serum of PC patients. Our validation test further suggested a relatively high accuracy of serum hsa-miR-21-5p levels in the diagnosis of PC, with a sensitivity of 0.77 and a specificity of 0.80. Finally, a diagnostic meta-analysis based on 9 studies also revealed favorable sensitivity and specificity of circulating hsa-miR-21-5p for the diagnosis of PC (pooled sensitivity and specificity were 0.76 and 0.74, respectively), which was consistent with our findings. Taken together, as one of the most aberrantly expressed miRNAs in PC, circulating hsa-miR-21-5p might be a promising serum biomarker in patients with PC.

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“…Multiple previous studies have demonstrated that the dysregulation of miRNAs is implicated in the occurrence and development of pancreatic cancer (26)(27)(28). Nevertheless, the detailed roles of miRNAs in pancreatic cancer and their underlying mechanisms of action remain largely unknown.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑584 directly targets CCND1 and inhibits cell proliferation and invasion in pancreatic cancer

Chen

et al. 2018

Mol Med Report

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Multiple previous studies have demonstrated that the dysregulation of microRNAs (miRNAs) is implicated in the occurrence and development of pancreatic cancer. Therefore, a further characterisation of deregulated miRNAs in pancreatic cancer may provide novel insight into the oncogenesis and progression of pancreatic cancer, which may facilitate the identification of effective therapeutic targets for treating patients with this disease. In the present study, reverse transcription-quantitative polymerase chain reaction analysis demonstrated that the expression level of miRNA-584-5p (miR-584) was significantly decreased in pancreatic cancer tissues and cell lines. It was demonstrated that restoration of miR-584 expression significantly suppressed the proliferative and invasive ability of pancreatic cancer cells. Bioinformatics analysis predicted that cyclin D1 (CCND1) was a putative target of miR-584. Subsequent experiments demonstrated that CCND1 was a direct target gene of miR-584 in pancreatic cancer cells. Furthermore, the inhibition of CCND1 mimicked the suppressive effect of miR-584 overexpression in pancreatic cancer cells. The restoration of CCND1 expression significantly abolished the inhibitory effects of miR-584 overexpression on pancreatic cancer cells. Collectively, the present results demonstrated that miR-584 inhibited the development of pancreatic cancer by directly targeting CCND1, suggesting that this miRNA may represent a potential therapeutic target for this fatal disease.

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Circulating microRNAs as diagnostic biomarkers for pancreatic cancer

Cited by 27 publications

References 34 publications

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

Circulating miRNA-21-5p as a diagnostic biomarker for pancreatic cancer: evidence from comprehensive miRNA expression profiling analysis and clinical validation

MicroRNA‑584 directly targets CCND1 and inhibits cell proliferation and invasion in pancreatic cancer

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