The Circulating Transcriptome as a Source of Biomarkers for Melanoma
The circulating transcriptome is a valuable source of cancer biomarkers, which, with the exception of microRNAs (miRNAs), remains relatively unexplored. To elucidate which RNAs are present in plasma from melanoma patients and which could be used to distinguish cancer patients from healthy individual...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-01-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6694/11/1/70 |
| _version_ | 1797707919322513408 |
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| author | Carla Solé Daniela Tramonti Maike Schramm Ibai Goicoechea María Armesto Luiza I. Hernandez Lorea Manterola Marta Fernandez-Mercado Karmele Mujika Anna Tuneu Ane Jaka Maitena Tellaetxe Marc R. Friedländer Xavier Estivill Paolo Piazza Pablo L. Ortiz-Romero Mark R. Middleton Charles H. Lawrie |
| author_facet | Carla Solé Daniela Tramonti Maike Schramm Ibai Goicoechea María Armesto Luiza I. Hernandez Lorea Manterola Marta Fernandez-Mercado Karmele Mujika Anna Tuneu Ane Jaka Maitena Tellaetxe Marc R. Friedländer Xavier Estivill Paolo Piazza Pablo L. Ortiz-Romero Mark R. Middleton Charles H. Lawrie |
| author_sort | Carla Solé |
| collection | DOAJ |
| description | The circulating transcriptome is a valuable source of cancer biomarkers, which, with the exception of microRNAs (miRNAs), remains relatively unexplored. To elucidate which RNAs are present in plasma from melanoma patients and which could be used to distinguish cancer patients from healthy individuals, we used next generation sequencing (NGS), and validation was carried out by qPCR and/or ddPCR. We identified 442 different microRNAs in samples, eleven of which were differentially expressed (p < 0.05). Levels of miR-134-5p and miR-320a-3p were significantly down-regulated (p < 0.001) in melanoma samples (n = 96) compared to healthy controls (n = 28). Differentially expressed protein-encoding mRNA 5′-fragments were enriched for the angiopoietin, p21-activated kinase (PAK), and EIF2 pathways. Levels of ATM1, AMFR, SOS1, and CD109 gene fragments were up-regulated (p < 0.001) in melanoma samples (n = 144) compared to healthy controls (n = 41) (AUC = 0.825). Over 40% of mapped reads were YRNAs, a class of non-coding RNAs that to date has been little explored. Expression levels of RNY3P1, RNY4P1, and RNY4P25 were significantly higher in patients with stage 0 disease than either healthy controls or more advanced stage disease (p < 0.001). In conclusion, we have identified a number of novel RNA biomarkers, which, most importantly, we validated in multi-center retrospective and prospective cohorts, suggesting potential diagnostic use of these RNA species. |
| first_indexed | 2024-03-12T06:14:39Z |
| format | Article |
| id | doaj.art-596accea6ba546c7bc2e430a7ef9ecab |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T06:14:39Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-596accea6ba546c7bc2e430a7ef9ecab2023-09-03T02:45:11ZengMDPI AGCancers2072-66942019-01-011117010.3390/cancers11010070cancers11010070The Circulating Transcriptome as a Source of Biomarkers for MelanomaCarla Solé0Daniela Tramonti1Maike Schramm2Ibai Goicoechea3María Armesto4Luiza I. Hernandez5Lorea Manterola6Marta Fernandez-Mercado7Karmele Mujika8Anna Tuneu9Ane Jaka10Maitena Tellaetxe11Marc R. Friedländer12Xavier Estivill13Paolo Piazza14Pablo L. Ortiz-Romero15Mark R. Middleton16Charles H. Lawrie17Molecular Oncology group, Biodonostia Research Institute, San Sebastián 20012, SpainDepartment of Oncology, University of Oxford, Oxford OX3 9DU, UKMolecular Oncology group, Biodonostia Research Institute, San Sebastián 20012, SpainMolecular Oncology group, Biodonostia Research Institute, San Sebastián 20012, SpainMolecular Oncology group, Biodonostia Research Institute, San Sebastián 20012, SpainMolecular Oncology group, Biodonostia Research Institute, San Sebastián 20012, SpainMolecular Oncology group, Biodonostia Research Institute, San Sebastián 20012, SpainMolecular Oncology group, Biodonostia Research Institute, San Sebastián 20012, SpainOnkologikoa-Oncology Institute Gipuzkoa, Gipuzkoa 20012, SpainDepartment of Dermatology, Hospital Universitario de Donostia, San Sebastian 20012, SpainDepartment of Dermatology, Hospital Universitario de Donostia, San Sebastian 20012, SpainMolecular Oncology group, Biodonostia Research Institute, San Sebastián 20012, SpainGenomics and Disease group, Centre for Genomic Regulation (CRG), Barcelona 08003, SpainGenomics and Disease group, Centre for Genomic Regulation (CRG), Barcelona 08003, SpainWellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UKDepartment of Dermatology, 12 de Octubre Hospital, Madrid 28041, SpainDepartment of Oncology, University of Oxford, Oxford OX3 9DU, UKMolecular Oncology group, Biodonostia Research Institute, San Sebastián 20012, SpainThe circulating transcriptome is a valuable source of cancer biomarkers, which, with the exception of microRNAs (miRNAs), remains relatively unexplored. To elucidate which RNAs are present in plasma from melanoma patients and which could be used to distinguish cancer patients from healthy individuals, we used next generation sequencing (NGS), and validation was carried out by qPCR and/or ddPCR. We identified 442 different microRNAs in samples, eleven of which were differentially expressed (p < 0.05). Levels of miR-134-5p and miR-320a-3p were significantly down-regulated (p < 0.001) in melanoma samples (n = 96) compared to healthy controls (n = 28). Differentially expressed protein-encoding mRNA 5′-fragments were enriched for the angiopoietin, p21-activated kinase (PAK), and EIF2 pathways. Levels of ATM1, AMFR, SOS1, and CD109 gene fragments were up-regulated (p < 0.001) in melanoma samples (n = 144) compared to healthy controls (n = 41) (AUC = 0.825). Over 40% of mapped reads were YRNAs, a class of non-coding RNAs that to date has been little explored. Expression levels of RNY3P1, RNY4P1, and RNY4P25 were significantly higher in patients with stage 0 disease than either healthy controls or more advanced stage disease (p < 0.001). In conclusion, we have identified a number of novel RNA biomarkers, which, most importantly, we validated in multi-center retrospective and prospective cohorts, suggesting potential diagnostic use of these RNA species.http://www.mdpi.com/2072-6694/11/1/70melanomaplasmaliquid biopsymiRNAmRNAbiomarkerYRNARNA species |
| spellingShingle | Carla Solé Daniela Tramonti Maike Schramm Ibai Goicoechea María Armesto Luiza I. Hernandez Lorea Manterola Marta Fernandez-Mercado Karmele Mujika Anna Tuneu Ane Jaka Maitena Tellaetxe Marc R. Friedländer Xavier Estivill Paolo Piazza Pablo L. Ortiz-Romero Mark R. Middleton Charles H. Lawrie The Circulating Transcriptome as a Source of Biomarkers for Melanoma Cancers melanoma plasma liquid biopsy miRNA mRNA biomarker YRNA RNA species |
| title | The Circulating Transcriptome as a Source of Biomarkers for Melanoma |
| title_full | The Circulating Transcriptome as a Source of Biomarkers for Melanoma |
| title_fullStr | The Circulating Transcriptome as a Source of Biomarkers for Melanoma |
| title_full_unstemmed | The Circulating Transcriptome as a Source of Biomarkers for Melanoma |
| title_short | The Circulating Transcriptome as a Source of Biomarkers for Melanoma |
| title_sort | circulating transcriptome as a source of biomarkers for melanoma |
| topic | melanoma plasma liquid biopsy miRNA mRNA biomarker YRNA RNA species |
| url | http://www.mdpi.com/2072-6694/11/1/70 |
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