ArticleJournal of clinical laboratory analysis2026
IGFBP3 As a Potential Biomarker and Therapeutic Target in Hepatocellular Carcinoma: A Multi-Cohort Analysis.
Article in Journal of clinical laboratory analysis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveThis study aimed to investigate the expression patterns and prognostic significance of insulin-like growth factor-binding protein 3 (IGFBP3) in hepatocellular carcinoma (HCC) and other cancer types.
methodsIGFBP3 expression was analyzed using The Cancer Genome Atlas (TCGA)-LIHC, International Cancer Genome Consortium (ICGC-LIRI-JP), Gene Expression Omnibus (GEO; GSE102079 and GSE112790), and Genotype-Tissue Expression (GTEx) databases. Experimental validation included immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) on 10 paired HCC tissues. Survival was assessed via Kaplan-Meier analysis in TCGA, ICGC, and 47-patient cohorts stratified by IGFBP3 immunoreactive score (IRS). Univariate and multivariate Cox regression identified prognostic factors. Immune infiltration correlations were evaluated using ESTIMATE and TIMER algorithms, with pan-cancer analysis conducted via TCGA database.
resultsIGFBP3 was significantly downregulated in HCC across all cohorts and validated in our cohort (p < 0.01). Elevated intratumoral IGFBP3 correlated with advanced tumor stage, high grade, and elevated AFP. High IGFBP3 predicted poorer overall survival in TCGA (HR = 1.666, p = 0.004) and ICGC (HR = 4.631, p = 0.0009), and was associated with shorter survival in our cohort (p = 0.0002). Multivariate analysis confirmed IGFBP3 as an independent prognostic factor (HR = 2.95, p = 0.014). IGFBP3 expression positively correlated with immunosuppressive cell infiltration (M2 macrophages, regulatory T cells) and enriched pathways including TGF-β and JAK-STAT signaling. Pan-cancer analysis revealed cancer-specific expression patterns, with HCC showing both overall downregulation and high-risk prognostic value in high-expression tumors.
conclusionIGFBP3 was low expression in HCC, yet high expression indicates poor prognosis. This suggests that IGFBP3 is a potential novel prognostic biomarker and therapeutic target in HCC.
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