A Comprehensive Pan-Cancer Analysis Revealing IGF2 Gene as a Diagnostic and Prognostic Biomarker

Cancer, one of the leading causes of mortality worldwide, is driven by genetic alterations promoting uncontrolled cell growth and metastasis. Among these genetic players, the insulin-like growth factor 2 (IGF2) gene has emerged as a significant factor in tumorigenesis. IGF2, a growth factor primarily produced in the liver, interacts with insulin and IGF receptors, influencing cell proliferation and survival. IGF2 is a known driver in fetal development and specific hepatic malignancies; its multi-omic diagnostic, prognostic, and immunological landscapes across diverse tissue barriers remain unmapped. This study presents a comprehensive pan-cancer analysis to systematically define the biomarker potential and epigenetic regulation of IGF2 across multiple human cancers.

We utilized various bioinformatic platforms, including Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and cBioPortal, to assess IGF2 gene expression and mutation profiles. Immune infiltration analysis evaluated IGF2's role in tumor-immune interactions. Gene expression data from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were analyzed, and findings were validated using the Gene Expression Omnibus (GEO). Kaplan-Meier survival analysis was applied to investigate the correlation between IGF2 expression and overall survival in different cancers.

IGF2 was significantly upregulated in cholangiocarcinoma (CHOL), liver hepatocellular carcinoma (LIHC), kidney chromophobe (KICH), and stomach adenocarcinoma (STAD) with P-values of 3.72E-05, 3.30-E08, 1.60E-03, and 1.43E-04, respectively. Survival analysis revealed that elevated IGF2 expression was associated with good prognosis in kidney renal papillary cell carcinoma (KIRP) (P = 7.2E-05). Immune infiltration analysis demonstrated a significant correlation between IGF2 expression and the presence of macrophages and CD4+ T cells in STAD (P = 1.30E-10, 2.61E-06, respectively), suggesting a role in modulating the tumor immune microenvironment. Genetic alterations in IGF2 were observed in multiple cancers, with missense mutations and deep deletions being the most prevalent. Patients with IGF2 mutations showed a trend toward poorer survival outcomes compared to those without mutations; however, the difference was not statistically significant (P = 0.384).

This study revealed that IGF2 plays a potential role as a diagnostic biomarker for CHOL, KICH, LIHC, and STAD and a prognostic biomarker role in KIRP.