IGFBP1 is a prognostic biomarker in esophageal carcinoma: mechanistic insights from bioinformatics profiling to in vitro functional validation

Abstract

Insulin-like growth factor binding protein 1 (IGFBP1) is documented as a pro- tumorigenic gene in various cancers; nevertheless, its specific function in esophageal carcinoma (ESCA) is unclear. This study used data obtained from The Cancer Genome Atlas (TCGA) to assess IGFBP1 expression, investigating its clinical outcome-related relevance, and explore its correlation in the context of ESCA tumor microenvironment. The Wilcoxon rank-sum test indicated a notable overexpression of IGFBP1 in ESCA compared to normal tissues, which was further validated via immunohistochemistry. Functional enrichment analysis identified tumor-related pathways, while ssGSEA/CIBERSORT methods linked IGFBP1 expression to altered immune infiltration. Furthermore, an investigation of single-cell data sourced from the GSE196756 data uncovered unique immune cell subsets linked to the expression of IGFBP1. The application of Cox regression alongside Kaplan-Meier survival analyses indicated that elevated levels of IGFBP1 were correlated with unfavorable outcomes in overall survival (OS), and disease-specific survival (DSS). Functional validation utilizing CCK-8 and transwell assays revealed that IGFBP1 silencing significantly suppressed the proliferative, invasive, and migratory capabilities of ESCA cell lines. Furthermore, in vivo analyses also presented similar results. Collectively, these results position IGFBP1 as a prognostic biomarker in ESCA, highlighting its functional involvement in tumor progression.