, Volume 22, Issue 3, pp 433–440 | Cite as

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

  • Ivana SullivanEmail author
  • Pau Riera
  • Marta Andrés
  • Albert Altés
  • Margarita Majem
  • Remei Blanco
  • Laia Capdevila
  • Andrés Barba
  • Agustí Barnadas
  • Juliana SalazarEmail author
Original Paper



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).


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].


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.


VEGF Genetic variants Metastatic NSCLC Prognostic factors 



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.

Compliance with ethical standards

Conflict of interest

The authors declared no conflict of interest.

Supplementary material

10456_2019_9668_MOESM1_ESM.docx (35 kb)
Supplementary material 1 (DOCX 34 kb)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Medical Oncology DepartmentHospital de la Santa Creu i Sant PauBarcelonaSpain
  2. 2.Genetics DepartmentHospital de la Santa Creu i Sant PauBarcelonaSpain
  3. 3.Pharmacy DepartmentHospital de la Santa Creu i Sant PauBarcelonaSpain
  4. 4.Faculty of Pharmacy and Food SciencesUniversitat de Barcelona (UB)BarcelonaSpain
  5. 5.Hematology DepartmentManresaSpain
  6. 6.Medical Oncology DepartmentConsorci Sanitari de Terrassa, Carretera de TorrebonicaTerrassaSpain
  7. 7.Medical Oncology DepartmentHospital de Sant Pau i Santa TeclaTarragonaSpain
  8. 8.Medicine DepartmentUniversitat Autònoma de Barcelona (UAB)Bellaterra (Cerdanyola del Vallès)Spain
  9. 9.CIBERER U-705, Hospital de la Santa Creu i Sant PauBarcelonaSpain

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