A Gene Signature Combining the Tissue Expression of Three Angiogenic Factors is a Prognostic Marker in Early-stage Non-small Cell Lung Cancer

• Published in: Annals of surgical oncology 2014-02, Vol.21 (2), p.612-620
• Main Authors: Sanmartín, Elena, Sirera, Rafael, Usó, Marta, Blasco, Ana, Gallach, Sandra, Figueroa, Santiago, Martínez, Nieves, Hernando, Cristina, Honguero, Antonio, Martorell, Miguel, Guijarro, Ricardo, Rosell, Rafael, Jantus-Lewintre, Eloisa, Camps, Carlos
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Angiogenesis Inducing Agents - metabolism; Biomarkers, Tumor - genetics; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Female; Follow-Up Studies; Humans; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Staging; Neovascularization, Pathologic - genetics; Oncology; Prognosis; Real-Time Polymerase Chain Reaction; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Surgery; Surgical Oncology; Survival Rate; Thoracic Oncology; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor B - genetics; Vascular Endothelial Growth Factor D - genetics
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-013-3330-x

Background Angiogenesis and lymphangiogenesis are key mechanisms for tumor growth and dissemination. They are mainly regulated by the vascular endothelial growth factor (VEGF) family of ligands and receptors. The aim of this study was to analyze relative expression levels of angiogenic markers in resectable non-small cell lung cancer patients in order to asses a prognostic signature that could improve characterization of patients with worse clinical outcomes. Methods RNA was obtained from tumor and normal lung specimens from 175 patients. Quantitative polymerase chain reaction was performed to analyze the relative expression of HIF1A, PlGF, VEGFA, VEGFA 165b , VEGFB, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, NRP1 and NRP2. Results Univariate analysis showed that tumor size and ECOG-PS are prognostic factors for time to progression (TTP) and overall survival (OS). This analysis in the case of angiogenic factors also revealed that PlGF, VEGFA, VEGFB and VEGFD distinguish patients with different outcomes. Taking into account the complex interplay between the different ligands of the VEGF family and to more precisely predict the outcome of the patients, we considered a new analysis combining several VEGF ligands. In order to find independent prognostic variables, we performed a multivariate Cox analysis, which showed that the subgroup of patients with higher relative expression of VEGFA plus lower VEGFB and VEGFD presented the poorest outcome for both TTP and OS. Conclusions The relative expression of these three genes can be considered as an angiogenic gene signature whose applicability for the selection of candidates for targeted therapies needs to be further validated.