Clinical Significance of Circulating miR-1273g-3p and miR-122-5p in Pancreatic Cancer
The burden of pancreatic cancer (PanC) requires innovation in the current diagnostic approach. This study aimed to uncover new circulating microRNAs (miRNAs) that would distinguish patients with PanC from healthy subjects (HS) compared with the cancer antigen 19-9 (CA 19-9), and predict patients...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-02-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.00044/full |
| _version_ | 1818386392178229248 |
|---|---|
| author | Tommaso Mazza Domenica Gioffreda Andrea Fontana Tommaso Biagini Massimo Carella Orazio Palumbo Evaristo Maiello Francesca Bazzocchi Angelo Andriulli Francesca Tavano |
| author_facet | Tommaso Mazza Domenica Gioffreda Andrea Fontana Tommaso Biagini Massimo Carella Orazio Palumbo Evaristo Maiello Francesca Bazzocchi Angelo Andriulli Francesca Tavano |
| author_sort | Tommaso Mazza |
| collection | DOAJ |
| description | The burden of pancreatic cancer (PanC) requires innovation in the current diagnostic approach. This study aimed to uncover new circulating microRNAs (miRNAs) that would distinguish patients with PanC from healthy subjects (HS) compared with the cancer antigen 19-9 (CA 19-9), and predict patients' clinical phenotypes and outcomes. MiRNA expression profiles in plasma were investigated by using a two-stage process. In a discovery phase, miRNAs levels were analyzed using the GeneChip™ miRNA 4.0 Affymetrix assay in 10 pools of plasma samples from PanC patients and HS; in a validation phase, significantly altered miRNAs were re-tested in independent cohorts of cancer patients and controls by droplet digital PCR (ddPCR). The diagnostic performance of the resulting miRNAs was compared to CA 19-9 determinations, and the associations of miRNAs plasma levels with patients' clinical phenotypes and outcomes were also taken into account. Bioinformatics selection of miRNAs differentially expressed in plasma uncovered miR-18a-5p, miR-122-5p, miR-1273g-3p, and miR-6126 as candidate oncogenic miRNAs in PanC. The ddPCR technology confirmed the significant over-expression of miR-122-5p, miR-1273g-3p, and miR-6126 in PanC compared to HS, in line with the trend of the CA 19-9 levels. Plasma levels of miR-1273g-3p, in combination with CA 19-9, showed higher power in distinguishing PanC patients from HS compared to the CA 19-9 tested alone, with a gain in both sensitivity and negative predictive value indicating a low false-negative rate (SE = 90.2% and NPV = 92.3% vs. SE = 82.1% and NPV = 87.9%). None of the oncogenic miRNAs were able to distinguish between a neoplastic and a proliferative/inflammatory disease of the pancreas, and were not able to stratify subjects according to the clinical risk for the disease. The only valuable association in PanC patients was found between miR-1273g-3p and tumor stage, and increased miR-122-5p levels emerged as independent negative prognostic factor for PanC patients (HR = 1.58, 95% CI = 1.03–2.43, p = 0.037). Our data highlighted a role for circulating miR-1273g-3p and miR-122-5p as new diagnostic and prognostic biomarkers for PanC. |
| first_indexed | 2024-12-14T03:53:19Z |
| format | Article |
| id | doaj.art-cf446459e1f5403eb9e73756c6218cc3 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-14T03:53:19Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-cf446459e1f5403eb9e73756c6218cc32022-12-21T23:18:10ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-02-011010.3389/fonc.2020.00044505582Clinical Significance of Circulating miR-1273g-3p and miR-122-5p in Pancreatic CancerTommaso Mazza0Domenica Gioffreda1Andrea Fontana2Tommaso Biagini3Massimo Carella4Orazio Palumbo5Evaristo Maiello6Francesca Bazzocchi7Angelo Andriulli8Francesca Tavano9Laboratory of Bioinformatics, Fondazione IRCCS Casa Sollievo della Sofferenza, Foggia, ItalyDivision of Gastroenterology and Research Laboratory, Fondazione IRCCS Casa Sollievo della, Foggia, ItalyUnit of Biostatistics, Fondazione IRCCS Casa Sollievo della Sofferenza, Foggia, ItalyLaboratory of Bioinformatics, Fondazione IRCCS Casa Sollievo della Sofferenza, Foggia, ItalyDivision of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, Foggia, ItalyDivision of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, Foggia, ItalyDepartment of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, Foggia, ItalyDepartment of Surgery, Fondazione IRCCS Casa Sollievo della Sofferenza, Foggia, ItalyDivision of Gastroenterology and Research Laboratory, Fondazione IRCCS Casa Sollievo della, Foggia, ItalyDivision of Gastroenterology and Research Laboratory, Fondazione IRCCS Casa Sollievo della, Foggia, ItalyThe burden of pancreatic cancer (PanC) requires innovation in the current diagnostic approach. This study aimed to uncover new circulating microRNAs (miRNAs) that would distinguish patients with PanC from healthy subjects (HS) compared with the cancer antigen 19-9 (CA 19-9), and predict patients' clinical phenotypes and outcomes. MiRNA expression profiles in plasma were investigated by using a two-stage process. In a discovery phase, miRNAs levels were analyzed using the GeneChip™ miRNA 4.0 Affymetrix assay in 10 pools of plasma samples from PanC patients and HS; in a validation phase, significantly altered miRNAs were re-tested in independent cohorts of cancer patients and controls by droplet digital PCR (ddPCR). The diagnostic performance of the resulting miRNAs was compared to CA 19-9 determinations, and the associations of miRNAs plasma levels with patients' clinical phenotypes and outcomes were also taken into account. Bioinformatics selection of miRNAs differentially expressed in plasma uncovered miR-18a-5p, miR-122-5p, miR-1273g-3p, and miR-6126 as candidate oncogenic miRNAs in PanC. The ddPCR technology confirmed the significant over-expression of miR-122-5p, miR-1273g-3p, and miR-6126 in PanC compared to HS, in line with the trend of the CA 19-9 levels. Plasma levels of miR-1273g-3p, in combination with CA 19-9, showed higher power in distinguishing PanC patients from HS compared to the CA 19-9 tested alone, with a gain in both sensitivity and negative predictive value indicating a low false-negative rate (SE = 90.2% and NPV = 92.3% vs. SE = 82.1% and NPV = 87.9%). None of the oncogenic miRNAs were able to distinguish between a neoplastic and a proliferative/inflammatory disease of the pancreas, and were not able to stratify subjects according to the clinical risk for the disease. The only valuable association in PanC patients was found between miR-1273g-3p and tumor stage, and increased miR-122-5p levels emerged as independent negative prognostic factor for PanC patients (HR = 1.58, 95% CI = 1.03–2.43, p = 0.037). Our data highlighted a role for circulating miR-1273g-3p and miR-122-5p as new diagnostic and prognostic biomarkers for PanC.https://www.frontiersin.org/article/10.3389/fonc.2020.00044/fullpancreatic cancercirculating microRNAexpression profilediagnostic performanceprognosis |
| spellingShingle | Tommaso Mazza Domenica Gioffreda Andrea Fontana Tommaso Biagini Massimo Carella Orazio Palumbo Evaristo Maiello Francesca Bazzocchi Angelo Andriulli Francesca Tavano Clinical Significance of Circulating miR-1273g-3p and miR-122-5p in Pancreatic Cancer Frontiers in Oncology pancreatic cancer circulating microRNA expression profile diagnostic performance prognosis |
| title | Clinical Significance of Circulating miR-1273g-3p and miR-122-5p in Pancreatic Cancer |
| title_full | Clinical Significance of Circulating miR-1273g-3p and miR-122-5p in Pancreatic Cancer |
| title_fullStr | Clinical Significance of Circulating miR-1273g-3p and miR-122-5p in Pancreatic Cancer |
| title_full_unstemmed | Clinical Significance of Circulating miR-1273g-3p and miR-122-5p in Pancreatic Cancer |
| title_short | Clinical Significance of Circulating miR-1273g-3p and miR-122-5p in Pancreatic Cancer |
| title_sort | clinical significance of circulating mir 1273g 3p and mir 122 5p in pancreatic cancer |
| topic | pancreatic cancer circulating microRNA expression profile diagnostic performance prognosis |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.00044/full |
| work_keys_str_mv | AT tommasomazza clinicalsignificanceofcirculatingmir1273g3pandmir1225pinpancreaticcancer AT domenicagioffreda clinicalsignificanceofcirculatingmir1273g3pandmir1225pinpancreaticcancer AT andreafontana clinicalsignificanceofcirculatingmir1273g3pandmir1225pinpancreaticcancer AT tommasobiagini clinicalsignificanceofcirculatingmir1273g3pandmir1225pinpancreaticcancer AT massimocarella clinicalsignificanceofcirculatingmir1273g3pandmir1225pinpancreaticcancer AT oraziopalumbo clinicalsignificanceofcirculatingmir1273g3pandmir1225pinpancreaticcancer AT evaristomaiello clinicalsignificanceofcirculatingmir1273g3pandmir1225pinpancreaticcancer AT francescabazzocchi clinicalsignificanceofcirculatingmir1273g3pandmir1225pinpancreaticcancer AT angeloandriulli clinicalsignificanceofcirculatingmir1273g3pandmir1225pinpancreaticcancer AT francescatavano clinicalsignificanceofcirculatingmir1273g3pandmir1225pinpancreaticcancer |