AUTHOR=Fan Dengxia , Yang Moses , Lee Hye Jung , Lee Jeong Hee , Kim Hong Sook 

TITLE=AVEN: a novel oncogenic biomarker with prognostic significance and implications of AVEN-associated immunophenotypes in lung adenocarcinoma

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1265359

DOI=10.3389/fmolb.2023.1265359

ISSN=2296-889X

ABSTRACT=AVEN, an apoptosis and caspase activation inhibitor, has been associated with adverse clinical outcomes and poor prognosis in Acute myeloid leukemia (AML). Targeting AVEN in AML improves apoptosis sensitivity and chemotherapy efficacy, making it a promising therapeutic target. However, AVEN's role has not been studied in solid tumors. Therefore, our study investigated AVEN as a prognostic biomarker in a more comprehensive manner and developed an AVEN-derived prognostic model in Lung adenocarcinoma (LUAD). AVEN expression was increased in several cancer types compared to normal tissue, but its impact on survival was only significant in LUAD in the TCGA cohort. High AVEN expression was significantly correlated with tumor progression and shorter life span in LUAD patients. Pathway analysis was performed with 838 genes associated with AVEN expression and several oncogenic pathways were altered such as Cell cycle, VEGFA-VEGFR2 pathway, and epithelial-mesenchymaltransition pathway. Immune infiltration was also analyzed, and less infiltrated B cells and CD4+ T cells were observed in AVEN high patients. Furthermore, an AVEN-derived genomic model was established, demonstrating a reliable and improved prognostic value in TCGA and GEO databases. This study provided evidence that AVEN is accumulated in LUAD compared to adjacent tissue and is associated with poor survival, high tumor progression, and immune infiltration alteration. Moreover, the study introduced the AVEN-derived prognostic model as a promising prognosis tool for LUAD.