Pan-cancer analysis reveal that m6A writer WTAP involve in tumor cell cycle regulation and tumor immunity.

Abstract

Background: Wilm's tumor 1-associated protein (WTAP) is a critical component of the methyltransferase complex responsible for N6-methyladenosine (m6A) modification in RNA. This modification is involved in various cancer-related biological processes. However, the precise role of WTAP in tumor cell cycle regulation and immune responses remains poorly understood.

Methods: A comprehensive analysis was conducted using multi-database resources to investigate the role of WTAP in tumorigenesis. Data from 33 tumor types were collected from the Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA), and Cancer Cell Line Encyclopedia (CCLE) databases. Correlations between WTAP expression and prognosis, immune microenvironment, immune neoantigens, immune checkpoint molecules, tumor mutation burden (TMB), and microsatellite instability (MSI) were analyzed. Additionally, Gene Set Enrichment Analysis (GSEA) was performed to explore the signaling pathways associated with WTAP expression.

Results: Pan-cancer analysis revealed differential expression of WTAP across multiple tumor types compared to normal tissues. High WTAP expression was significantly associated with poor prognosis in adrenocortical carcinoma (ACC), brain lower-grade glioma (LGG), liver hepatocellular carcinoma (LIHC), and ovarian serous cystadenocarcinoma (OV). In contrast, low WTAP expression correlated with improved survival in skin cutaneous melanoma (SKCM) and thymoma (THYM). WTAP expression demonstrated a positive correlation with immune cell infiltration, including B cells, CD4 + T cells, CD8 + T cells, dendritic cells, macrophages, and neutrophils. Additionally, WTAP expression was positively associated with stromal, immune, and overall immune estimate scores. No significant association was identified between WTAP expression and immune neoantigen counts. However, WTAP expression correlated with the expression of most common immune checkpoint genes, DNA mismatch repair genes, and DNA methyltransferases. Furthermore, WTAP expression significantly influenced TMB and MSI levels. GSEA indicated that WTAP predominantly contributes to cell cycle regulation, thereby promoting tumorigenesis.

Conclusion: WTAP is a potential immune-related prognostic biomarker in malignancies. Its role in regulating the cell cycle and immune microenvironment highlights its influence on tumor development and progression.