Bo Yin,* Huijuan Zhou* 

Department of Gynecology; Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Huijuan Zhou, Email zhouhuijuan@51mch.com

Introduction: Ovarian cancer (OC) ranks among the most lethal and aggressive gynecological malignancies. Identifying novel molecular targets is crucial for improving early diagnosis and developing effective therapies. Despite advancements in immunotherapy, its efficacy in OC remains limited due to the absence of well-defined immune-related molecular targets.
Methods: This study offers a comprehensive analysis of YTHDF1, combining multi-omics-based bioinformatics approaches with in vitro and in vivo experimental validation to elucidate its functional role and significance in the progression and treatment of OC.
Results: Our findings reveal that YTHDF1 is significantly upregulated in OC and correlates with poor clinical outcomes. Functional assays confirmed its oncogenic properties, while pathway analyses highlight its involvement in critical tumor-promoting signaling pathways. Importantly, we identified a potential link between YTHDF1 expression and the tumor immune landscape, suggesting its role in modulating immune cell infiltration and driving immunosuppression. Additionally, both computational and in vivo evidence underline the relevance of YTHDF1 in influencing immunotherapeutic responsiveness and chemosensitivity in OC. Mechanistically, we discovered for the first time that YTHDF1 can be encapsulated within tumor-derived exosomes, contributing to the polarization of macrophages toward the immunosuppressive M2a phenotype.
Discussion: These findings position YTHDF1 as a promising prognostic biomarker and therapeutic target for OC. Its role in shaping an immunosuppressive microenvironment and mediating chemoresistance underscores its potential in enhancing immunotherapy and improving chemotherapy outcomes.

Keywords: ovarian cancer, YTHDF1, biomarker, therapeutic target, macrophage