Circulating miR-16-5p, miR-92a-3p, and miR-451a in Plasma from Lung Cancer Patients: Potential Application in Early Detection and a Regulatory Role in Tumorigenesis Pathways
Background: Micro(mi)RNAs, potent gene expression regulators associated with tumorigenesis, are stable, abundant circulating molecules, and detectable in plasma. Thus, miRNAs could potentially be useful in early lung cancer detection. We aimed to identify circulating miRNA signatures in plasma from...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/8/2071 |
| _version_ | 1797561214289575936 |
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| author | Patricia P. Reis Sandra A. Drigo Robson F. Carvalho Rainer Marco Lopez Lapa Tainara F. Felix Devalben Patel Dangxiao Cheng Melania Pintilie Geoffrey Liu Ming-Sound Tsao |
| author_facet | Patricia P. Reis Sandra A. Drigo Robson F. Carvalho Rainer Marco Lopez Lapa Tainara F. Felix Devalben Patel Dangxiao Cheng Melania Pintilie Geoffrey Liu Ming-Sound Tsao |
| author_sort | Patricia P. Reis |
| collection | DOAJ |
| description | Background: Micro(mi)RNAs, potent gene expression regulators associated with tumorigenesis, are stable, abundant circulating molecules, and detectable in plasma. Thus, miRNAs could potentially be useful in early lung cancer detection. We aimed to identify circulating miRNA signatures in plasma from patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and to verify whether miRNAs regulate lung oncogenesis pathways. Methods: RNA isolated from 139 plasma samples (40 LUAD, 38 LUSC; 61 healthy/non-diseased individuals) were divided into discovery (38 patients; 21 controls for expression quantification using an 800-miRNA panel; Nanostring nCounter<sup>®</sup>) and validation (40 patients; 40 controls; TaqMan<sup>®</sup> RT-qPCR) cohorts. Elastic net, Maximizing-R-Square Analysis (MARSA), and C-Statistics were applied for miRNA signature identification. Results: When compared to healthy individuals, 580 of 606 deregulated miRNAs in LUAD and 221 of 226 deregulated miRNAs in LUSC had significantly increased levels. Among the 10 most significantly overexpressed miRNAs, 6 were common to patients with LUAD and LUSC. Further analysis identified three signatures composed of 12 miRNAs. Signatures included miRNAs commonly overexpressed in patient plasma. Enriched pathways included target genes modulated by three miRNAs in the C-Statistics signature: miR-16-5p, miR-92a-3p, and miR-451a. Conclusions: The 3-miRNA signature (miR-16-5p, miR-92a-3p, miR-451a) had high specificity (100%) and sensitivity (84%) to predict cancer (LUAD and LUSC). These miRNAs are predicted to modulate genes and pathways with known roles in lung tumorigenesis, including <i>EGFR</i>, <i>K-RAS</i>, and <i>PI3K/AKT</i> signaling, suggesting that the 3-miRNA signature is biologically relevant in adenocarcinoma and squamous cell carcinoma of the lung. |
| first_indexed | 2024-03-10T18:10:56Z |
| format | Article |
| id | doaj.art-3db81e13c9ca402289bda05cf4e0ae00 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:10:56Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-3db81e13c9ca402289bda05cf4e0ae002023-11-20T08:04:30ZengMDPI AGCancers2072-66942020-07-01128207110.3390/cancers12082071Circulating miR-16-5p, miR-92a-3p, and miR-451a in Plasma from Lung Cancer Patients: Potential Application in Early Detection and a Regulatory Role in Tumorigenesis PathwaysPatricia P. Reis0Sandra A. Drigo1Robson F. Carvalho2Rainer Marco Lopez Lapa3Tainara F. Felix4Devalben Patel5Dangxiao Cheng6Melania Pintilie7Geoffrey Liu8Ming-Sound Tsao9Faculty of Medicine, São Paulo State University, UNESP, Botucatu, SP 18618-687, BrazilFaculty of Medicine, São Paulo State University, UNESP, Botucatu, SP 18618-687, BrazilDepartment of Structural and Functional Biology, Institute of Biosciences, São Paulo State University, UNESP, Botucatu, SP 18618-689, BrazilUniversidad Católica Los Ángeles de Chimbote, Instituto de Investigación, Chimbote 02800, PeruFaculty of Medicine, São Paulo State University, UNESP, Botucatu, SP 18618-687, BrazilPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, CanadaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, CanadaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, CanadaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, CanadaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, CanadaBackground: Micro(mi)RNAs, potent gene expression regulators associated with tumorigenesis, are stable, abundant circulating molecules, and detectable in plasma. Thus, miRNAs could potentially be useful in early lung cancer detection. We aimed to identify circulating miRNA signatures in plasma from patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and to verify whether miRNAs regulate lung oncogenesis pathways. Methods: RNA isolated from 139 plasma samples (40 LUAD, 38 LUSC; 61 healthy/non-diseased individuals) were divided into discovery (38 patients; 21 controls for expression quantification using an 800-miRNA panel; Nanostring nCounter<sup>®</sup>) and validation (40 patients; 40 controls; TaqMan<sup>®</sup> RT-qPCR) cohorts. Elastic net, Maximizing-R-Square Analysis (MARSA), and C-Statistics were applied for miRNA signature identification. Results: When compared to healthy individuals, 580 of 606 deregulated miRNAs in LUAD and 221 of 226 deregulated miRNAs in LUSC had significantly increased levels. Among the 10 most significantly overexpressed miRNAs, 6 were common to patients with LUAD and LUSC. Further analysis identified three signatures composed of 12 miRNAs. Signatures included miRNAs commonly overexpressed in patient plasma. Enriched pathways included target genes modulated by three miRNAs in the C-Statistics signature: miR-16-5p, miR-92a-3p, and miR-451a. Conclusions: The 3-miRNA signature (miR-16-5p, miR-92a-3p, miR-451a) had high specificity (100%) and sensitivity (84%) to predict cancer (LUAD and LUSC). These miRNAs are predicted to modulate genes and pathways with known roles in lung tumorigenesis, including <i>EGFR</i>, <i>K-RAS</i>, and <i>PI3K/AKT</i> signaling, suggesting that the 3-miRNA signature is biologically relevant in adenocarcinoma and squamous cell carcinoma of the lung.https://www.mdpi.com/2072-6694/12/8/2071lung cancerlung adenocarcinomalung squamous cell carcinomamicroRNAsplasmaliquid biopsy |
| spellingShingle | Patricia P. Reis Sandra A. Drigo Robson F. Carvalho Rainer Marco Lopez Lapa Tainara F. Felix Devalben Patel Dangxiao Cheng Melania Pintilie Geoffrey Liu Ming-Sound Tsao Circulating miR-16-5p, miR-92a-3p, and miR-451a in Plasma from Lung Cancer Patients: Potential Application in Early Detection and a Regulatory Role in Tumorigenesis Pathways Cancers lung cancer lung adenocarcinoma lung squamous cell carcinoma microRNAs plasma liquid biopsy |
| title | Circulating miR-16-5p, miR-92a-3p, and miR-451a in Plasma from Lung Cancer Patients: Potential Application in Early Detection and a Regulatory Role in Tumorigenesis Pathways |
| title_full | Circulating miR-16-5p, miR-92a-3p, and miR-451a in Plasma from Lung Cancer Patients: Potential Application in Early Detection and a Regulatory Role in Tumorigenesis Pathways |
| title_fullStr | Circulating miR-16-5p, miR-92a-3p, and miR-451a in Plasma from Lung Cancer Patients: Potential Application in Early Detection and a Regulatory Role in Tumorigenesis Pathways |
| title_full_unstemmed | Circulating miR-16-5p, miR-92a-3p, and miR-451a in Plasma from Lung Cancer Patients: Potential Application in Early Detection and a Regulatory Role in Tumorigenesis Pathways |
| title_short | Circulating miR-16-5p, miR-92a-3p, and miR-451a in Plasma from Lung Cancer Patients: Potential Application in Early Detection and a Regulatory Role in Tumorigenesis Pathways |
| title_sort | circulating mir 16 5p mir 92a 3p and mir 451a in plasma from lung cancer patients potential application in early detection and a regulatory role in tumorigenesis pathways |
| topic | lung cancer lung adenocarcinoma lung squamous cell carcinoma microRNAs plasma liquid biopsy |
| url | https://www.mdpi.com/2072-6694/12/8/2071 |
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