Increased VEGF‑A in solid type of lung adenocarcinoma reduces the patients’ survival

Abstract

The histological classifcation of lung adenocarcinoma includes 5 types: lepidic, acinar, papillary, micropapillary and solid. The complex gene interactions and anticancer immune response of these types are not well known. The aim of this study was to reveal the survival rates, genetic alterations and immune activities of the fve histological types and provide treatment strategies. This study reviewed the histological fndings of 517 patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database and classifed them into fve types. We performed gene set enrichment analysis (GSEA) and survival analysis according to the diferent types. We found six oncogenic gene sets that were higher in lung adenocarcinoma than in normal tissues. In the survival analysis of each type, the acinar type had a favorable prognosis, and the solid subtype had an unfavorable prognosis; however, the survival diferences between the other types were not signifcant. Our study focused on the solid type, which had the poorest prognosis. The solid type was related to adaptive immune resistance associated with elevated CD8 T cells and high CD274 (encoding PD-L1) expression. In the pathway analyses, the solid type was signifcantly related to high vascular endothelial growth factor (VEGF)-A expression, refecting tumor angiogenesis. Non-necrosis/low immune response afected by high VEGF-A was associated with worse prognosis. The solid type associated with high VEGF-A expression may contribute to the development of therapeutic strategies for lung adenocarcinoma.