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

Abstract

The histological classification 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 five histological types and provide treatment strategies. This study reviewed the histological findings of 517 patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database and classified them into five types. We performed gene set enrichment analysis (GSEA) and survival analysis according to the different 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 differences between the other types were not significant. 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 significantly related to high vascular endothelial growth factor (VEGF)-A expression, reflecting tumor angiogenesis. Non-necrosis/low immune response affected 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.

Correlation between the Expression of VEGF and Ki67 and Lymph Node Metastasis in Non-small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

“…VEGF is a family in which VEGF-A can accelerate angiogenesis and increase the permeability of blood vessels [ 49 ]. VEGF-C and VEGF-D function in angiogenesis and new lymphatic vessels in cancer tissues [ 26 ].…”

Iloprost requires the Frizzled-9 receptor to prevent lung cancer

“…Vegf, which is associated with reduced survival in lung adenocarcinoma patients, was decreased in adenomas with iloprost in wild type mice but increased in Fzd 9 −/− iloprost-treated mice ( Jung et al., 2021 ; Naikoo et al., 2017 ). Although Esr2 is predominantly expressed in lung tissue and lung tumors, we only detected changes in Esr1 in adenomas from our mouse model ( Liau et al., 2021 ).…”

Palmar Fasciitis and Polyarthritis Syndrome Associated with Lung Adenocarcinoma

“…Considering the association with ovarian cancer, these cytokines are thought to play an important role in the progression of PFPAS. The expression of TGF-β, IGF, and VEGF is also found in lung cancer ( 8 - 10 ), and TGF-β is associated with metastasis of lung cancer ( 8 ).…”