Characterization of the Biochemical Recurrence Prediction Ability and Progression Correlation of Peroxiredoxins Family in Prostate Cancer Based on Integrating Single-Cell RNA-Seq and Bulk RNA-Seq Cohorts

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-04-25 DOI:10.1002/cam4.70855

Shan Tang, Jinchuang Li, Weicheng Tian, Yuanfa Feng, Yulin Deng, Zeheng Tan, Zhaodong Han, Huichan He, Yongding Wu, Chuyang Huang, Keping Ning, Feng Liu, Hongwei Luo, Shanghua Cai, Jianheng Ye, Weide Zhong

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Abstract

Introduction

The peroxiredoxins (PRDXs) family plays a crucial role in balancing reactive oxygen species (ROS) levels in tumor cells. However, its potential role in prognosis and therapy response of prostate cancer (PCa) remains unknown.

Methods

In this study, we utilized 2 public single-cell RNA datasets and 8 bulk-RNA datasets to investigate the clinical value of six PRDXs family members in PCa. Expression comparison, biochemical recurrence analysis, and therapy response analysis were measured. Pathway enrichments were utilized to predict the potential down-stream pathway it may involve. In vitro experiments were used to validate the function of PRDX5 in the progression of castration-resistant prostate cancer (CRPC) cell lines.

Result

Among the PRDXs family, PRDX5 was most related to the advancement of prostate cancer. A nomogram integrating the expression of PRDX5 with clinical features was developed to better predict clinical outcomes in PCa patients compared to 30 published signatures. Immunohistochemistry was used to verify that PRDX5 expression was higher in advanced levels of PCa tissue. Gene Set Enrichment Analysis (GSEA) and pathway predictive analysis revealed that the PRDX5 related genes were mainly relevant to ROS Pathway, Mitochondria-related functions, cellular respiration, and oxidative phosphorylation. In vitro cell proliferation assays, ROS determination assay, and apoptosis assay together revealed that depletion of PRDX5 induces apoptosis via ROS accumulation in CRPC cells. Moreover, the expression of PRDX5 in CRPC cells also affects the sensitivity to the ARSI therapy.

Conclusion

This study offers new evidence for determining that the expression of PRDX5 is associated with advanced tumor grade, poor prognosis, and suboptimal response to multiple therapies in PCa within the PRDXs family. Last but not least, our study provides new insights into precision medicine in PCa and provides a reference for further research on PRDX5.

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基于整合单细胞RNA-Seq和整体RNA-Seq队列的前列腺癌过氧化物还毒素家族生化复发预测能力及进展相关性研究

过氧化物还毒素（PRDXs）家族在平衡肿瘤细胞中的活性氧（ROS）水平方面起着至关重要的作用。然而，其在前列腺癌（PCa）预后和治疗反应中的潜在作用尚不清楚。方法利用2个公开的单细胞RNA数据集和8个大体积RNA数据集，研究6个prdx家族成员在PCa中的临床价值。进行表达比较、生化复发分析、治疗效果分析。途径富集被用来预测它可能涉及的潜在下游途径。体外实验验证了PRDX5在去势抵抗性前列腺癌（CRPC）细胞系进展中的作用。结果prdx家族中，PRDX5与前列腺癌的进展关系最为密切。将PRDX5的表达与临床特征相结合的nomogram （nomogram）可以更好地预测PCa患者的临床结果，与30个已发表的特征相比较。免疫组织化学证实PRDX5在晚期前列腺癌组织中表达较高。基因集富集分析（Gene Set Enrichment Analysis， GSEA）和通路预测分析显示，PRDX5相关基因主要与ROS通路、线粒体相关功能、细胞呼吸和氧化磷酸化相关。体外细胞增殖实验、ROS测定实验和细胞凋亡实验共同表明，PRDX5的缺失通过ROS积累诱导CRPC细胞凋亡。此外，PRDX5在CRPC细胞中的表达也会影响对ARSI治疗的敏感性。结论本研究为PRDX5家族前列腺癌中PRDX5的表达与晚期肿瘤分级、不良预后和对多种治疗的次优反应相关提供了新的证据。最后，我们的研究为PCa的精准医学提供了新的见解，并为PRDX5的进一步研究提供了参考。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.