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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1446894
This article is part of the Research Topic Genomic Discoveries and Pharmaceutical Development in Urologic Tumors View all 15 articles

Anoikis in Prostate Cancer Bone Metastasis Gene Signatures and Therapeutic Implications

Provisionally accepted
Wei Xia Wei Xia 1*Miao Ye Miao Ye 2Bo Jiang Bo Jiang 1Gang Xu Gang Xu 1Guancheng Xiao Guancheng Xiao 1Qingming Zeng Qingming Zeng 1Ruohui Huang Ruohui Huang 1
  • 1 Department of Urology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
  • 2 Breast Diagnosis and Treatment Center, First Affiliated Hospital of Gannan Medical University, Ganzhou, China

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

    Bone metastasis from prostate cancer severely impacts patient outcomes and quality of life. Anoikis, a form of programmed cell death triggered by the loss of cell-matrix interactions, plays a critical role in cancer progression. However, its precise relationship with prostate cancer-induced bone metastasis remains unclear. This study aims to elucidate this relationship, focusing on anoikis-related gene signatures, molecular pathways, and therapeutic implications.We used the TCGA-PRAD dataset for training, with MSKCC and GSE70769 as validation cohorts. To evaluate immunotherapy efficacy, we examined IMvigor 210 and GSE91016 datasets, and GSE137829 provided single-cell insights into prostate cancer. Specific anoikis-related genes (ARGs) were identified, and Random Survival Forest analysis and multivariate Cox regression were employed to develop anoikis-linked features. The 'clustanoikisProfilanoikis' and 'GSEA' packages were used to explore potential ARG-related pathways.Analyzing 553 samples from TCGA, 231 from MSKCC, 94 from GSE70769, and single-cell data from 6 prostate cancer patients (GSE137829), we constructed a prognostic model based on 9 ARGs. GSVA revealed upregulation of carcinogenic pathways, including epithelial-mesenchymal transition, E2F targets, and angiogenesis, with downregulation of metabolic pathways. Significant differences in somatic mutations were observed between cohorts, with a positive correlation between anoikis scores and tumor mutational burden (TMB). Immune landscape analysis suggested high-risk patients might benefit more from chemotherapy than immunotherapy based on their risk score. Single-cell analysis indicated overactivation of carcinogenic pathways in the high anoikis score group.This study elucidates the complex interplay between anoikis and bone metastasis in prostate cancer. Our findings highlight the critical role of anoikis in metastatic progression, enhancing the understanding of key biomarkers and molecular dynamics. The identified anoikis-related gene signatures and disrupted pathways offer promising avenues for predictive and therapeutic strategies in prostate cancer management.

    Keywords: prostate cancer, Anoikis, Model, bioinformatics, metastasis 1

    Received: 10 Jun 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Xia, Ye, Jiang, Xu, Xiao, Zeng and Huang. 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: Wei Xia, Department of Urology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China

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