IGF2BP2 Overexpression Predicts Poor Prognosis and Correlates with PD-L1 Expression in Intrahepatic Cholangiocarcinoma.

Background

The immunologically cold nature and immunosuppressive tumor microenvironment (TME) of intrahepatic cholangiocarcinoma (ICC) contribute to its poor prognosis. This study aims to identify novel biomarkers related to prognosis and TME in ICC.

Methods

We first identified the high expression of m6A reader insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) in ICC through bioinformatics screening. Subsequently, a retrospective study was conducted on 224 ICC patients who had undergone radical resection. The expression levels of IGF2BP2 and programmed death ligand 1 (PD-L1) were detected in a tissue microarray (TMA) using immunohistochemistry (IHC). The co-localization of IGF2BP2, PD-L1, programmed cell death protein 1 (PD-1), and CD8+T cells was evaluated by multiple immunofluorescence techniques.

Results

IHC confirmed a significant upregulation of IGF2BP2 in tumor tissues compared with normal bile duct epithelia (p < 0.05). IGF2BP2 expression was positively correlated with PD-L1 expression (TPS R = 0.215, p = 0.016; CPS R = 0.295, p = 0.008). High IGF2BP2 expression was associated with increased PD-L1/PD-1 positivity and reduced CD8+T cell infiltration. Kaplan-Meier analysis revealed significantly worse 3-year overall survival (OS: 20.56% vs. 29.91%, p = 0.0291) and recurrence-free survival (RFS: 9.72% vs. 18.56%, p = 0.0372) in the IGF2BP2-high group. Multivariate analysis identified IGF2BP2 as an independent risk factor for both OS (HR = 1.683, p = 0.044) and RFS (HR = 1.946, p = 0.042).

Conclusions

IGF2BP2, as a potential biomarker and independent prognostic factor for ICC, is associated with increased PD-L1 expression.