Gallach-Garcia, S.; Jantus-Lewintre, E.; Calabuig-Fariñas, S.; Montaner, D.; Alonso, S.; Sirera Pérez, R.; Blasco, A.... (2017). MicroRNA profiling associated with non-small cell lung cancer: next generation sequencing detection, experimental validation, and prognostic value. Oncotarget. 8(34):56143-56157. https://doi.org/10.18632/oncotarget.18603
Por favor, use este identificador para citar o enlazar este ítem: http://hdl.handle.net/10251/148251
Title:
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MicroRNA profiling associated with non-small cell lung cancer: next generation sequencing detection, experimental validation, and prognostic value
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Author:
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Gallach-Garcia, Sandra
Jantus-Lewintre, Eloisa
Calabuig-Fariñas, Silvia
Montaner, David
Alonso, Sergio
Sirera Pérez, Rafael
Blasco, Ana
Usó-Marco, Marta
Guijarro, Ricardo
Martorell, Miguel
Camps-Herrero, Carlos
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UPV Unit:
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Universitat Politècnica de València. Departamento de Biotecnología - Departament de Biotecnologia
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Issued date:
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Abstract:
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[EN] Background: The average five-year survival for non-small cell lung cancer (NSCLC) patients is approximately 15%. Emerging evidence indicates that microRNAs (miRNAs) constitute a new class of gene regulators in humans ...[+]
[EN] Background: The average five-year survival for non-small cell lung cancer (NSCLC) patients is approximately 15%. Emerging evidence indicates that microRNAs (miRNAs) constitute a new class of gene regulators in humans that may play an important role in tumorigenesis. Hence, there is growing interest in studying their role as possible new biomarkers whose expression is aberrant in cancer. Therefore, in this study we identified dysregulated miRNAs by next generation sequencing (NGS) and analyzed their prognostic value.
Methods: Sequencing by oligo ligation detection technology was used to identify dysregulated miRNAs in a training cohort comprising paired tumor/normal tissue samples (N = 32). We validated 22 randomly selected differentially-expressed miRNAs by quantitative real time PCR in tumor and adjacent normal tissue samples (N = 178). Kaplan-Meier survival analysis and Cox regression were used in multivariate analysis to identify independent prognostic biomarkers.
Results: NGS analysis revealed that 39 miRNAs were dysregulated in NSCLC: 28 were upregulated and 11 were downregulated. Twenty-two miRNAs were validated in an independent cohort. Interestingly, the group of patients with high expression of both miRNAs (miR-21(high) and miR-188(high)) showed shorter relapse-free survival (RFS) and overall survival (OS) times. Multivariate analysis confirmed that this combined signature is an independent prognostic marker for RFS and OS (p = 0.001 and p < 0.0001, respectively).
Conclusions: NGS technology can specifically identify dysregulated miRNA profiles in resectable NSCLC samples. MiR-21 or miR-188 overexpression correlated with a negative prognosis, and their combined signature may represent a new independent prognostic biomarker for RFS and OS.
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Subjects:
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MicroRNAs
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NSCLC
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NGS
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Profiling
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Prognosis
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Copyrigths:
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Reconocimiento (by)
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Source:
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Oncotarget. (eissn:
1949-2553
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DOI:
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10.18632/oncotarget.18603
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Publisher:
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Impact Journals, LLC
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Publisher version:
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https://doi.org/10.18632/oncotarget.18603
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Project ID:
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info:eu-repo/grantAgreement/MINECO//RD12%2F0036%2F0025/ES/Cáncer/
info:eu-repo/grantAgreement/MINECO//PI12%2F02838/ES/Identificación de biomarcadores moleculares asociados a células madre tumorales en cáncer de pulmón no microcítico. Implicación en el desarrollo de nuevas estrategias terapéuticas/
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Thanks:
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This work was supported by the RD12/0036/0025 and RD06/0020/1024 PI12-02838, ISCIII, grants from the Fondo Europeo de Desarrollo Regional (FEDER), by funds from the Proyecto de Investigacion Fundamental Orientada a la ...[+]
This work was supported by the RD12/0036/0025 and RD06/0020/1024 PI12-02838, ISCIII, grants from the Fondo Europeo de Desarrollo Regional (FEDER), by funds from the Proyecto de Investigacion Fundamental Orientada a la Transmision de Conocimiento a la Empresa (TRACE; TRA09-0132) and Beca Roche Oncohematologia.
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Type:
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Artículo
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