Revisiting IGF2BP1 in Endometrial Cancer: Ethnic-Specific Prognostic Implications and Association with Caspase-3 and pSTAT3

<b>Background:</b> Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) has emerged as a key N6-methyladenosine reader protein involved in RNA stability and oncogenesis across various cancers. Previous studies, primarily based on Western cohorts, have associated high IGF2BP1 expression with poor prognosis and aggressive tumor behavior in endometrial cancer (EC). However, the prognostic significance of IGF2BP1 in East Asian populations, including those from Taiwan, remains unclear. <b>Methods:</b> This retrospective study analyzed 75 paraffin-embedded EC tissue samples from treatment-naïve Taiwanese patients. Immunohistochemical staining was performed to assess IGF2BP1 expression. Patients were categorized into high- and low-expression groups based on a receiver operating characteristic-derived cutoff score of 10. Kaplan-Meier survival analysis and log-rank tests were used to evaluate survival outcomes. Univariable and multivariable logistic regression analyses were employed to explore associations with clinicopathological features and key biomarkers, including caspase-3 and phosphorylated signal transducer and activator of transcription 3 (pSTAT3). <b>Results:</b> Contrary to prior literature, patients with high IGF2BP1 expression (score >10) exhibited significantly better overall survival compared to the low-expression group (log-rank p = 0.029). The high-expression group-maintained survival probabilities above 85% throughout the 4-year follow-up period, while the low-expression group declined below 40%. Furthermore, high IGF2BP1 expression was positively correlated with caspase-3, a key pro-apoptotic marker, and negatively correlated with pSTAT3, a well-known inflammatory and oncogenic signal transducer. These findings suggest that IGF2BP1 may exert context-dependent biological functions in EC, potentially promoting apoptosis and dampening tumor-promoting inflammation in Taiwanese patients. <b>Conclusion:</b> This study provides novel evidence that high IGF2BP1 expression is associated with improved prognosis in Taiwanese patients with EC. These findings highlight potential ethnic differences in IGF2BP1-mediated tumor biology, suggesting that IGF2BP1 may serve as a favorable prognostic biomarker and therapeutic target. Further mechanistic and population-based studies are warranted to clarify its dualistic role in endometrial tumorigenesis.