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Insulin-like growth factor binding protein-3 serves as a biomarker for resistance to enzalutamide in prostate cancer
Ze Gao1, Bingzheng An1, Shuo Chen2
1Department of Urology, Qilu Hospital of Shandong University, Jinan, China.
Abstract:
Enzalutamide resistance (EnzR) is a major challenge in the current treatment of castration-resistant prostate cancer, as tumors frequently progress to drug resistance after an initially effective treatment. Therefore, there is an urgent need to characterize the genes alterations that accompany EnzR in prostate cancer and to identify new therapeutic targets. In this study, we analyzed a total of 1273 publicly available transcriptomics datasets from patients who underwent prostate cancer surgery. We investigated transcriptomic changes after enzalutamide (ENZ) treatment, identified key genes involved in the process of EnzR, and developed EnzR scores to predict tumor progression. We further investigated the role of IGFBP3 in the regulation of EnzR in prostate cancer. The effect of IGFBP3 expression level on the malignant degree of EnzR cells was explored in vitro. In addition, we explored the downstream mechanism of IGFBP3 involvement in EnzR. We found that epithelial-mesenchymal transition (EMT), cancer stem cell-like properties, and neuroendocrine transformation occurred in tumor cells after ENZ treatment. Subsequently, we developed and validated EnzR scores to predict prostate cancer tumor progression. Furthermore, we experimentally confirmed that IGFBP3 promotes the proliferation of drug-resistant cells and enhances ENZ resistance via EMT signaling. Overall, we established a new EnzR scoring model through multidimensional analysis of EnzR patterns. This model can accurately predict the clinical prognosis of prostate cancer patients after surgery. Moreover, IGFBP3 can be used as a potential therapeutic target for ENZ resistance in prostate cancer.
Insights
Enzalutamide resistance (EnzR) in prostate cancer is a challenge. This study identifies IGFBP3 as a key driver of EnzR and develops a scoring model to predict patient prognosis.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Enzalutamide resistance (EnzR) is a significant clinical challenge in castration-resistant prostate cancer (CRPC).
- Tumor progression to drug resistance necessitates identification of novel therapeutic targets and predictive biomarkers.
- Understanding the molecular mechanisms underlying EnzR is crucial for improving patient outcomes.
Purpose of the Study:
- To characterize transcriptomic alterations associated with EnzR in prostate cancer.
- To identify key genes and pathways involved in EnzR.
- To develop a predictive model for EnzR and explore IGFBP3 as a therapeutic target.
Main Methods:
- Analysis of 1273 publicly available transcriptomics datasets from prostate cancer patients.
- Investigation of transcriptomic changes following enzalutamide (ENZ) treatment.
- In vitro experiments to assess the role of IGFBP3 in EnzR and its downstream mechanisms.
- Development and validation of an EnzR scoring model.
Main Results:
- Identified epithelial-mesenchymal transition (EMT), cancer stem cell-like properties, and neuroendocrine transformation in ENZ-treated tumors.
- Developed and validated EnzR scores for predicting tumor progression and clinical prognosis.
- Confirmed that IGFBP3 promotes proliferation of drug-resistant cells and enhances EnzR via EMT signaling.
- Established IGFBP3 as a potential therapeutic target for overcoming ENZ resistance.
Conclusions:
- A novel EnzR scoring model accurately predicts prostate cancer prognosis post-surgery.
- IGFBP3 plays a critical role in promoting EnzR through EMT signaling.
- Targeting IGFBP3 presents a promising strategy for managing enzalutamide-resistant prostate cancer.
