Dataset Information

Novel Circulating miRNA Signatures for Early Detection of Pancreatic Neoplasia.

ABSTRACT:

Objectives

Pancreatic ductal adenocarcinoma (PDAC) presents the lowest survival rate of all cancers because only 6% of patients reach five-year survival. Alterations in the expression of several microRNAs (miRNAs) occur in the tumor of PDAC and in preneoplastic lesions as the called intraductal papillary mucinous neoplasm (IPMN). Here, we aimed at identifying which miRNAs are significantly altered in liquid biopsies from patients with PDAC and IPMN to find new noninvasive biomarkers for early detection of PDAC.

Methods

We analyzed by real-time quantitative reverse transcription-PCR (qRT-PCR) the expression of 17 circulating miRNAs, previously found to be significantly overexpressed in tissue pancreatic neoplasms, in a set of 182 plasma samples (94 PDAC, 19 IPMN, 18 chronic pancreatitis, and 51 disease-free controls). Then, we analyzed CA19.9 levels in the same plasma set, and we assessed the diagnostic values of differentially expressed miRNAs, CA19.9, and all possible combinations.

Results

Of note, 16, 14, and 9 miRNAs were significantly increased in PDAC, IPMN, and chronic pancreatitis, respectively, compared with control plasmas. miR-21-5p, miR-33a-3p, miR-320a, and miR-93-5p showed the highest discriminating capacity for pancreatic neoplasia (PDAC or IPMN) with an area under the receiver operating characteristic curve (AUC) of 0.86, 0.85, 0.85, and 0.80, respectively. 2-miRNA combinations improved these performances reaching AUC = 0.90 for "miR-33a-3p+miR-320a." Addition of CA19.9 increased the diagnostic potential of miRNA signatures even further achieving an AUC of 0.95 (93% sensitivity and 85% specificity) for the combination of "miR-33a-3p+miR-320a+CA19.9."

Conclusions

Novel signatures combining miRNAs and CA19.9 could be used as noninvasive biomarkers for early detection of PDAC.

SUBMITTER: Vila-Navarro E

PROVIDER: S-EPMC6602779 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Novel Circulating miRNA Signatures for Early Detection of Pancreatic Neoplasia.

Vila-Navarro Elena E Duran-Sanchon Saray S Vila-Casadesús Maria M Moreira Leticia L Ginès Àngels À Cuatrecasas Miriam M Lozano Juan José JJ Bujanda Luis L Castells Antoni A Gironella Meritxell M

Clinical and translational gastroenterology 20190401 4

<h4>Objectives</h4>Pancreatic ductal adenocarcinoma (PDAC) presents the lowest survival rate of all cancers because only 6% of patients reach five-year survival. Alterations in the expression of several microRNAs (miRNAs) occur in the tumor of PDAC and in preneoplastic lesions as the called intraductal papillary mucinous neoplasm (IPMN). Here, we aimed at identifying which miRNAs are significantly altered in liquid biopsies from patients with PDAC and IPMN to find new noninvasive biomarkers for ...[more]

PMID: 31009404

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Project description:Currently, the majority of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) present with locally invasive and/or metastatic disease, resulting in five-year survival of less than 5%. The development of an early diagnostic test is, therefore, expected to significantly impact the patient's prognosis. In this study, we successfully evaluated the feasibility of identifying diagnostic cell free microRNAs (miRNAs) for early stage PDAC, through the analysis of urine samples. Using Affymetrix microarrays, we established a global miRNA profile of 13 PDAC, six chronic pancreatitis (CP), and seven healthy (H) urine specimens. Selected differentially expressed miRNAs were subsequently investigated using an independent technique (RT-PCR) on 101 urine samples including 46 PDAC, 29 CP and 26 H. Receiver operating characteristic (ROC) and logistic regression analyses were applied to determine the discriminatory potential of the candidate miRNA biomarkers. Three miRNAs (miR-143, miR-223, and miR-30e) were significantly over-expressed in patients with Stage I cancer when compared with age-matched healthy individuals (P=0.022, 0.035 and 0.04, respectively); miR-143, miR-223 and miR-204 were also shown to be expressed at higher levels in Stage I compared to Stages II-IV PDAC (P=0.025, 0.013 and 0.008, respectively). Furthermore, miR-223 and miR-204 were able to distinguish patients with early stage cancer from patients with CP (P=0.037 and 0.036). Among the three biomarkers, miR-143 was best able to differentiate Stage I (n=6) from healthy (n=26) with area under the curve (AUC) of 0.862 (95% CI 0.695-1.000), with sensitivity (SN) of 83.3% (95% CI 50.0-100.0), and specificity (SP) of 88.5% (95% CI 73.1-100.0). The combination of miR-143 with miR-30e was significantly better at discriminating between these two groups, achieving an AUC of 0.923 (95% CI 0.793-1.000), with SN of 83.3% (95% CI 50.0-100.0) and SP of 96.2% (95% CI 88.5-100.0). In this feasibility study, we demonstrate for the first time the utility of miRNA biomarkers for non-invasive, early detection of PDAC in urine specimens.

Dataset Information

Novel Circulating miRNA Signatures for Early Detection of Pancreatic Neoplasia.

Objectives

Methods

Results

Conclusions

Publications

Novel Circulating miRNA Signatures for Early Detection of Pancreatic Neoplasia.

Similar Datasets

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