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Prognostic effect of VEGF gene variants in metastatic non-small-cell lung cancer patients

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Abstract

Introduction

Clinical and pathological characteristics are still considered prognostic markers in metastatic non-small-cell lung cancer (NSCLC) patients but they cannot explain all interindividual variability. Tumoral angiogenesis mediated by the vascular endothelial growth factor (VEGF) is critical for the progression and metastasis of the disease. We aimed to investigate the prognostic role of genetic variants within the VEGF pathway in patients with metastatic NSCLC.

Materials and methods

We prospectively included 170 patients with metastatic NSCLC treated with first-line platinum-based chemotherapy. A comprehensive panel of single-nucleotide polymorphisms (SNPs) in genes belonging to the VEGF pathway (VEGFA, VEGFR1/FLT1, VEGFR2/KDR, GRB2, ITGAV, KISS1, KRAS, PRKCE, HIF1α, MAP2K4, MAP2K6, and MAPK11) were genotyped in blood DNA samples. SNPs were evaluated for association with overall survival (OS) and progression-free survival (PFS).

Results

In multivariate analyses adjusted for patient characteristics, we found that VEGFA rs2010963 and VEGFR2 rs2071559 were significantly associated with OS [Hazard Ratio (HR) 0.7 (0.5–0.9); p = 0.026 and HR 1.5 (1.1–2.3); p = 0.025, respectively]. Additionally, ITGAV rs35251833 and MAPK11 rs2076139 were significantly associated with PFS [HR 2.5 (1.4–4.3; p = 0.002 and HR 0.6 (0.5–0.9); p = 0.013, respectively].

Conclusion

Our findings reinforce the potential clinical value of germline variants in VEGFA and VEGFR2 and show for the first time variants in ITGAV and MAPK11 as promising prognostic markers in metastatic NSCLC patients receiving platinum-based chemotherapy.

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Acknowledgements

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. We thank Carolyn Newey for language editing.

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Author notes

  1. Ivana Sullivan and Pau Riera contributed equally to this study.

Authors and Affiliations

  1. Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Sant Quintí, 89, 08041, Barcelona, Spain

    Ivana Sullivan, Marta Andrés, Margarita Majem, Andrés Barba & Agustí Barnadas

  2. Genetics Department, Hospital de la Santa Creu i Sant Pau, Sant Quintí, 89, 08041, Barcelona, Spain

    Pau Riera & Juliana Salazar

  3. Pharmacy Department, Hospital de la Santa Creu i Sant Pau, Sant Quintí, 89, 08041, Barcelona, Spain

    Pau Riera

  4. Faculty of Pharmacy and Food Sciences, Universitat de Barcelona (UB), Campus Diagonal, Av. de Joan XXIII, 27-31, 08028, Barcelona, Spain

    Pau Riera

  5. Hematology Department, Fundació Althaia, C/Dr. Joan Soler, 1-3, 08243, Manresa, Barcelona, Spain

    Albert Altés

  6. Medical Oncology Department, Consorci Sanitari de Terrassa, Carretera de Torrebonica, S/N, 08227, Terrassa, Spain

    Remei Blanco

  7. Medical Oncology Department, Hospital de Sant Pau i Santa Tecla, Rambla Vella, 14, 43003, Tarragona, Spain

    Laia Capdevila

  8. Medicine Department, Universitat Autònoma de Barcelona (UAB), Edifici M. Av. de Can Domènech, 08193, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain

    Agustí Barnadas

  9. CIBERER U-705, Hospital de la Santa Creu i Sant Pau, Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain

    Juliana Salazar

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  1. Ivana Sullivan
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  2. Pau Riera
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Sullivan, I., Riera, P., Andrés, M. et al. Prognostic effect of VEGF gene variants in metastatic non-small-cell lung cancer patients. Angiogenesis 22, 433–440 (2019). https://doi.org/10.1007/s10456-019-09668-y

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  • DOI: https://doi.org/10.1007/s10456-019-09668-y

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