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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Cancer Imaging and Image-directed Interventions

This article is part of the Research TopicAdvancing Cancer Imaging Technologies: Bridging the Gap from Research to Clinical Practice Volume IIView all 16 articles

Predicting HER2 Overexpression in Prostate Cancer Using Machine Learning: Implications for Personalized Therapy

Provisionally accepted
  • 1Nanjing Drum Tower Hospital, Nanjing, China
  • 2Nanjing University Medical School, Nanjing, China

The final, formatted version of the article will be published soon.

BACKGROUND: Human Epidermal Growth Factor Receptor 2 (HER2), a component of the epidermal growth factor receptor family, is thought to be related to advanced prostate cancer (PCa) when overexpressed. Currently, most research on HER2 is limited to molecular pathology, with relatively few studies focused on imaging aspects. OBJECTIVES: To develop a predictive model by extracting high-throughput radiomics features from magnetic resonance imaging and combining them with clinical characteristics for predicting HER2 overexpression. MATERIALS AND METHODS: A total of 201 patients who underwent radical prostatectomy and HER2 immunohistochemistry were retrospectively enrolled. These patients were randomly divided into a training set (n=160) and a test set (n=41). Multimodal radiomics features extracted from T2-weighted imaging (T2WI) and apparent diffusion coefficient maps (ADC) were selected using Mann-Whitney U test and least absolute shrinkage and selection operator (LASSO) with ten-fold cross-validation. Predictive models were developed and evaluated based on discrimination and clinical utility. RESULTS: The combined model integrating ISUP Grade, PSA and Radscore achieved an area under the curve (AUC) of 0.841 (95% CI: 0.697-0.955) in the test set, significantly outperforming the clinical model (AUC = 0.580; p = 0.02, DeLong test) and demonstrating a modest improvement over the Radscore model (AUC = 0.838 (0.693-0.951). Evaluation results showed consistent discriminatory power: 0.78 accuracy, 0.77 sensitivity, and 0.79 specificity, indicating well-balanced performance between positive and negative classes. Decision curve analysis and Waterfall plot demonstrated strong clinical applicability. CONCLUSION: The combined model effectively predicts HER2 overexpression in prostate cancer, with potential to inform more personalized treatment strategies for HER2-overexpressing PCa patients.

Keywords: HER2, machine learning, Magnetic Resonance Imaging, prostate cancer, Radiomics

Received: 18 Sep 2025; Accepted: 17 Dec 2025.

Copyright: © 2025 Huang, Gao, Wang, Li, Zhang, Guo and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Qing Zhang
Hong Qian Guo
Xiaozhi Zhao

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