Oncotarget

Research Papers:

MicroRNA profiling associated with non-small cell lung cancer: next generation sequencing detection, experimental validation, and prognostic value

Sandra Gallach, Eloisa Jantus-Lewintre _, Silvia Calabuig-Fariñas, David Montaner, Sergio Alonso, Rafael Sirera, Ana Blasco, Marta Usó, Ricardo Guijarro, Miguel Martorell and Carlos Camps

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Oncotarget. 2017; 8:56143-56157. https://doi.org/10.18632/oncotarget.18603

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Abstract

Sandra Gallach1,2, Eloisa Jantus-Lewintre1,2,3, Silvia Calabuig-Fariñas1,2,4, David Montaner5, Sergio Alonso6, Rafael Sirera2,3, Ana Blasco2,7, Marta Usó1, Ricardo Guijarro8,9, Miguel Martorell4,10 and Carlos Camps1,2,7,11

1 Molecular Oncology Laboratory, Fundación Investigación, Hospital General Universitario de Valencia, Valencia, Spain

2 Centro de Investigación Biomédica en Red de Cáncer (CIBEROnc), Madrid, Spain

3 Department of Biotechnology, Universitat Politècnica de València, Valencia, Spain

4 Department of Pathology, Universitat de València, Valencia, Spain

5 Department of Computational Genomics, Centro de Investigación Príncipe Felipe, Valencia, Spain

6 Program of Predictive and Personalized Medicine of Cancer, Institut de Reserca Germans Trias i Pujol (PMPPC-IGTP), Badalona, Spain

7 Department of Medical Oncology, Hospital General Universitario de Valencia, Valencia, Spain

8 Department of Surgery, Universitat de València, Valencia, Spain

9 Department of Thoracic Surgery, Hospital General Universitario de Valencia, Valencia, Spain

10 Department of Pathology, Hospital General Universitario de Valencia, Valencia, Spain

11 Department of Medicine, Universitat de València, Valencia, Spain

Correspondence to:

Eloisa Jantus-Lewintre, email:

Carlos Camps, email:

Keywords: microRNAs, NSCLC, NGS, profiling, prognosis

Received: May 09, 2017 Accepted: June 09, 2017 Published: June 22, 2017

Abstract

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-21high and miR-188high) 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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