Deciphering the multidimensional impact of IGFBP1 expression on cancer prognosis, genetic alterations, and cellular functionality: A comprehensive Pan-cancer analysis.

ABSTRACT

Objectives: IGF-binding protein 1 (IGFBP1) is a key regulator of insulin-like growth factors, impacting biological processes, including cancer progression and prognosis. Materials and methods: This study investigates genetic alterations affecting IGFBP1 expression in tumors using data from The Cancer Genome Atlas (TCGA) PanCancer Atlas via cBioPortal. We analyzed samples from 32 cancer types for mutation sites, including deep deletions, amplifications, and mutations. RNA-seq data were normalized using log2(value + 1). Statistical analyses, including survival outcomes, were conducted using R packages like ggplot2, stats, and car. Kaplan-Meier survival curves and log-rank tests assessed overall survival (OS) and progression-free survival (PFS). Univariate Cox regression was used to develop nomogram models for OS. Functional consequences of IGFBP1 mutations were explored through protein structure, stability, and IGF interaction analyses. Protein-protein interaction networks and functional enrichment were analyzed using GEPIA2, STRING, and Cytoscape. Gene Ontology (GO), KEGG, and Gene Set Enrichment Analysis (GSEA) provided insights into affected biological pathways. Results: Pan-cancer analysis revealed diverse expression patterns, including significant upregulation in cutaneous melanoma (SKCM) and downregulation in lung adenocarcinoma (LUAD) and stomach adenocarcinoma (STAD). Specifically, elevated IGFBP1 expression in SKCM patients led to a 25 % improvement in 5-year survival. In contrast, higher IGFBP1 levels in LUAD and OV patients resulted in a 30 % and 20 % decrease in survival, respectively. Elevated IGFBP1 levels are significantly linked to advanced tumor stage and grade in OV and LUAD, affecting prognostic outcomes. Nomogram models for OV, SKCM, LUAD, and STAD showed IGFBP1's predictive strength with AUC values ranging from 0.70 to 0.85, indicating its diagnostic potential. Genetic analyses revealed mutations in IGFBP1 in 12 % of STAD cases and 10 % of UCEC cases, indicating significant genetic variation. Immune analysis showed that high IGFBP1 expression significantly influenced immune cell infiltration, particularly macrophages and CD8+ T cells, thereby affecting survival in LUAD and OV. Functional enrichment and gene set enrichment analysis identified IGFBP1 involvement in crucial pathways, such as cell cycle regulation, immune response, and PD-1 signaling, highlighting its biological impact. Additionally, IGFBP1 expression delineates distinct molecular and immune subtypes, correlating with specific cancer behaviors and immune patterns. Conclusions: These findings highlight IGFBP1's potential as a biomarker and therapeutic target, particularly for immunoregulation and cancer subtype stratification.