title: Prognostic significance of combining VEGFA, FLT1 and KDR mRNA expression in lung cancer.
abstract: Angiogenesis is important in cancer progression. Promising results in clinical trials have indicated that targeting vascular epidermal growth factor (VEGF) signaling may prolong lung cancer patient survival. In particular, various studies have implicated VEGFA as a potential prognostic marker in lung cancer, although prognostication using the expression of VEGF receptors (VEGFRs), such as fms-related tyrosine kinase 1 (FLT1; also known as VEGFR1) and kinase insert domain receptor (KDR; also known as VEGFR2), has produced varied results in different lung cancer studies. The present study aimed to investigate the prognostic significance of these three factors, alone or in combination. mRNA expression data were extracted from four independent lung cancer cohorts totaling 583 patients, and the association between mRNA expression and survival was investigated by performing statistical analyses. When VEGFA, FLT1 and KDR expression were considered alone, only VEGFA demonstrated a significant association with patient survival consistently across all four datasets (P<0.05). Patients with a high expression of VEGFA and one of the two receptors were associated with significantly worse survival than patients expressing low levels of VEGFA and the particular receptor (P<0.05). Notably, patients with a high level expression of all three genes in their tumor specimens were associated with a significantly shorter survival time compared with patients exhibiting a low level expression of one, two or all three genes (P<0.05). The results indicate that a high level of VEGFA expression and its receptors may be required for cancer progression. Therefore, these three factors should be considered together as a prognostic indicator for lung cancer patients.
authors.affiliation: Faculty of Health Sciences (E12), University of Macau, Macau SAR, P.R. China ; Center for Cancer Research and Cell Biology and School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Shu-Dong
authors.initials: SD
authors.lastname: Zhang
authors.affiliation: Center for Cancer Research and Cell Biology and School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Cian M
authors.initials: CM
authors.lastname: McCrudden
authors.affiliation: Faculty of Health Sciences (E12), University of Macau, Macau SAR, P.R. China ; Center for Cancer Research and Cell Biology and School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK ; Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK.
authors.forename: Hang Fai
authors.initials: HF
authors.lastname: Kwok
keywords: angiogenesis; fms-related tyrosine kinase 1; kinase insert domain receptor; lung cancer; survival; vascular epidermal growth factor A