Transcriptomic Profiles for Elucidating Response of Bladder Intracavitary Hyperthermic Perfusion Chemotherapy in High-Risk Nonmuscular Invasive Bladder Cancer

IF 3.1 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2025-02-20 DOI:10.1002/cam4.70672

Zhicheng Huang, Tianhui Zhang, Jinghua Pan, Guihao Zhang, Linjun Jiang, Huiming Jiang, Pei Wan, Ying Peng, Wenchao Zou, Qinghua Liu, Nanhui Chen

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Abstract

Background

Bladder intracavitary hyperthermic perfusion chemotherapy (HIPEC) is a promising treatment for non-muscular invasive bladder cancer (NMIBC). However, the molecular mechanisms underlying the response to HIPEC remain poorly understood. This study aimed to elucidate the transcriptomic profiles associated with the response to HIPEC in NMIBC patients.

Methods

RNA sequencing was performed on bladder tumor samples from NMIBC patients who underwent HIPEC treatment. Differentially expressed genes (DEGs) between responders and non-responders to HIPEC were identified. Gene ontology and pathway analysis were conducted to explore the biological functions and pathways enriched in the DEGs. Additionally, the expression of specific immune-related genes was evaluated for their association with HIPEC response. The diagnostic efficiency of selected genes in predicting relapse before and after HIPEC treatment was assessed in a validation cohort.

Results

We assessed the expression status of differentially expressed genes (DEGs) between responders and non-responders to HIPEC. Gene ontology and pathway analysis revealed that DEGs were enriched in immune-related pathways, including cytokine-cytokine receptor interaction, chemokine signaling pathway, and antigen processing and presentation. Furthermore, the expression of several immune-related genes, including ZMAP4, UPP2, and GALR1, was significantly associated with the response to HIPEC. Therefore, the immune system's reaction plays a crucial role in the response to HIPEC in patients with NMIBC. At last, a considerable diagnostic efficiency that tissue TMEFF2, KRT222, and GTSF1 in predicting relapse in NMIBC patients after HIPEC treatment, and ZMAP4, UPP2, and GALR1 in predicting relapse in NMIBC patients before HIPEC treatment in the validation cohort.

Conclusion

Transcriptomic profiling revealed that immune-related pathways and genes play a crucial role in the response to HIPEC in NMIBC patients. These findings suggest that transcriptomic profiling could provide a valuable tool for predicting treatment outcomes and identifying therapeutic targets for NMIBC.

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表达膀胱腔内热灌注化疗对高危非肌性浸润性膀胱癌疗效的转录组学分析

膀胱腔内热灌注化疗（HIPEC）是治疗非肌性浸润性膀胱癌（NMIBC）的一种很有前途的治疗方法。然而，对HIPEC反应的分子机制仍然知之甚少。本研究旨在阐明与NMIBC患者对HIPEC反应相关的转录组谱。方法对HIPEC治疗的NMIBC患者膀胱肿瘤标本进行RNA测序。鉴定了HIPEC应答者和非应答者之间的差异表达基因（DEGs）。通过基因本体论和途径分析，探索deg丰富的生物学功能和途径。此外，我们还评估了特异性免疫相关基因的表达与HIPEC反应的关系。在一个验证队列中评估了选定基因在预测HIPEC治疗前后复发方面的诊断效率。结果我们评估了HIPEC反应者和非反应者之间差异表达基因（DEGs）的表达状况。基因本体和通路分析显示，DEGs富集于免疫相关通路，包括细胞因子-细胞因子受体相互作用、趋化因子信号通路、抗原加工和递呈等。此外，包括ZMAP4、UPP2和GALR1在内的几个免疫相关基因的表达与HIPEC应答显著相关。因此，免疫系统的反应在NMIBC患者对HIPEC的反应中起着至关重要的作用。最后，在验证队列中，组织TMEFF2、KRT222和GTSF1在预测HIPEC治疗前NMIBC患者复发方面具有相当高的诊断效率，ZMAP4、UPP2和GALR1在预测HIPEC治疗前NMIBC患者复发方面具有相当高的诊断效率。结论转录组学分析表明，免疫相关途径和基因在NMIBC患者对HIPEC的反应中起着至关重要的作用。这些发现表明，转录组学分析可以为预测NMIBC的治疗结果和确定治疗靶点提供有价值的工具。

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.