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Decoding the Homeobox (HOX) Gene Expression Profile: Implications for Diagnosis, Prognosis and Survival in Prostate Cancer

This article is a preprint and has not been certified by peer review.

Authors

    Wang Liu,  
    Wang Liu
    Shuai Tang,  
    Shuai Tang
    Moben Mirza,  
    Moben Mirza
    Benyi Li
    Benyi Li
Categories
Cell Biology
Keywords
HOX genes; gene expression; RNAseq data; prostate cancer; disease prognosis

Abstract

Objectives: This study provides a comprehensive analysis of the expression profiles and clinical significance of homeobox (HOX) genes in prostate cancer (PCa).

Methods: We utilized large-scale datasets including TCGA-PRAD, DKFZ-RNAseq, and metastatic castration-resistant prostate cancer (mCRPC) cohorts. We screened 228 HOX-related genes for gene expression related to disease progression, diagnosis, and prognosis. Gene expression was compared in patient subgroups stratified by clinical parameters. Survival prognosis was analyzed using the Kaplan-Meier survival curve approach. The AUC value of the altered gene was determined using the Receiver Operating Characteristic (ROC) curve analysis. The effect of castration on HOX-related gene expression was analyzed using the LuCaP35 xenograft dataset.

Results: We identified 42 up-regulated and 56 down-regulated genes with significant differential expression between benign and malignant tissues. Further investigation into 22 key genes revealed their profound impact on diagnosis and prognosis. HOXC6 and NKX2-3 emerged as highly effective diagnostic biomarkers, demonstrating area under the curve (AUC) values of 0.917 and 0.936, respectively. Prognostically, NKX6-1 expression showed the strongest predictive potential for 5-year disease-specific survival (AUC = 0.881), while HOXB7 also served as a critical survival indicator (AUC = 0.909). Conversely, the down-regulation of EVX2 was uniquely associated with all clinicopathological and survival parameters, suggesting a significant tumor-suppressive role. In early-onset PCa, HOXC5, HOXC6, and MEIS2 correlated strongly with tumor mutation burden and biochemical recurrence. In the context of advanced disease, NKX2-3 was associated with Androgen Receptor (AR) activation scores, whereas MEIS2 showed a strong negative correlation. Notably, this study identified HOXB8/HOXD13 genes, like LHX2, as novel and consistent markers, significantly increased in treatment-induced neuroendocrine prostate cancer (t-NEPC).

Conclusion: These findings highlight a distinct subset of HOX genes that govern prostate cancer progression and provide a framework for developing novel diagnostic and prognostic tools tailored to disease stage and subtype.

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DOI:

https://doi.org/10.65215/LTSpreprints.2026.05.03.000222

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2026-05-03

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Liu, W., Tang, S., Mirza, M., & Li, B. (2026). Decoding the Homeobox (HOX) Gene Expression Profile: Implications for Diagnosis, Prognosis and Survival in Prostate Cancer. LangTaoSha Preprint Server. https://doi.org/10.65215/LTSpreprints.2026.05.03.000222

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