221P - ANGPTL4's role in cancer: A meta analysis and bioinformatics exploration

Background

Angiopoietin-like protein 4 (ANGPTL4) plays a crucial role in processes such as angiogenesis, inflammation, and metabolism. Despite numerous studies suggesting its involvement in cancer, a definitive role remains unclear. We introduce the first comprehensive meta-analysis and pan-cancer bioinformatic study on ANGPTL4, aiming to unravel its implications across various cancer types.

Methods

Moderate-to high-quality observational studies were retrieved from PubMed, Scopus, and Embase. A meta-analysis was conducted using Review Manager (version 5.4) and the R package “metafor.” Survival analysis was performed using GEPIA2 and TIMER2.0. Immune infiltration, mutational burden, and drug resistance analyses was done via GSCAlite. Co-expression and gene set enrichment analyses (GSEA) were carried out using cBioportal and enrichr, respectively.

Results

The pooled results showed that elevated ANGPTL4 worsened clinicopathological factors, including Tumor Grade (OR = 1.51, P= 0.023), stage (OR = 2.42, P<0.001), lymph node metastasis (OR = 1.76, P=0.012), vascular invasion (OR = 2.16, P=0.01), and lymphatic invasion (OR = 2.20, P<0.001). Overall survival (OS) and Disease-free survival were insignificant. Multivariate analysis of TCGA cohort showed significantly worse OS for CESC (HR=1.2), GBM (HR=1.12), LGG (HR=1.35), LUAD (HR=1.13), MESO (HR=1.22), OV (HR=1.16), STAD (HR=1.16), and UCS (HR=1.27). However, better OS was observed in SKCM (HR=0.913). Single gene level analysis revealed that ANGPTL4 upregulated epithelial-to-mesenchymal transition (EMT) in 11/33 cancers. Immune infiltration varied between different cancers, but increased infiltration of cancer-associated fibroblasts was observed in most cancers. Mutation analysis revealed increased alterations in TP53 and CDKN2A in cohorts with ANGPTL4 alterations. GSEA of co-expressed genes revealed involvement in hypoxia, EMT, VEGF-A complex, and extracellular matrix organization.

Conclusions

ANGPTL4’s role in cancer varies among different cancers, but an overall oncogenic effect can be hypothesized from its involvement in EMT, angiogenesis, metastasis, and worse overall survival outcomes. Further studies exploring the biological variance of ANGPTL4 are required to confirm these results.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.