Transcriptome analysis of ovarian cancer uncovers association between tumor-related inflammation/immunity and patient outcome.

IF 4.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY Frontiers in Pharmacology Pub Date : 2025-02-06 eCollection Date: 2025-01-01 DOI:10.3389/fphar.2025.1500251
Jingfang Wang, Wenrui Zhu, Xia Li, Yuanyuan Wu, Wenhui Ma, Yangzhou Wang, Weihong Zhao, Fang Wei, Wenhao Wang
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Abstract

Background: Epithelial ovarian cancer (EOC) is a cancer that affects the female reproductive system and is highly lethal. It poses significant challenges in terms of treatment and often has a poor prognosis. In recent years, with the advent of PARPi, the treatment of ovarian cancer has entered a new stage of full-process management. Although more and more drugs have been approved, the therapeutic effect of PARPi is still very limited. With the rapid development of PD-1/PD-L1, CTLA-4, oncolytic viruses, cancer vaccines, adoptive cell therapy, etc., tumor immunotherapy has provided new opportunities for the treatment of ovarian cancer.

Methods: This study used comprehensive transcriptome analysis across multiple databases to gather gene transcripts and clinical features of normal ovarian samples and tissue samples from ovarian cancer. The aim was to explore the mechanisms underlying tumor immunotherapy resistance and to reveal the relationship between ovarian cancer's immune microenvironment and genes linked to inflammation. Various R packages were used for differential gene analysis, enrichment analysis, co-expression network construction, and prognostic model building.

Results: It has been found that the prognosis of ovarian cancer patients is closely associated with sets of genes involved in inflammation. The immune infiltration microenvironment, clinicopathological features, and survival rates differed significantly between two inflammatory gene expression patterns identified using cluster and immune microenvironment analyses. Further analysis revealed that the high-risk group had a higher abundance of M2-type macrophage infiltration, more active anti-tumor immune response, higher tumor stemness score, potentially worse prognosis, and lower response rates to multiple chemotherapy drugs and immune checkpoint inhibitors.

Conclusion: These findings provide new perspectives and potential targets for immunotherapy and prognostic evaluation of ovarian cancer and offer new strategies and directions for clinical treatment and patient management. This study provides crucial information to further our comprehension of drug response mechanisms and tumor immunotherapy. It offers new strategies and methods for the treatment and prognostic improvement of ovarian cancer.

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卵巢癌转录组分析揭示肿瘤相关炎症/免疫与患者预后之间的关联。
背景:上皮性卵巢癌(EOC)是一种影响女性生殖系统的高致死率癌症。它在治疗方面提出了重大挑战,往往预后不良。近年来,随着PARPi的出现,卵巢癌的治疗进入了全流程管理的新阶段。虽然越来越多的药物被批准,但PARPi的治疗效果仍然非常有限。随着PD-1/PD-L1、CTLA-4、溶瘤病毒、肿瘤疫苗、过继细胞治疗等的快速发展,肿瘤免疫治疗为卵巢癌的治疗提供了新的契机。方法:本研究利用多个数据库的综合转录组分析,收集正常卵巢样本和卵巢癌组织样本的基因转录本和临床特征。目的是探索肿瘤免疫治疗抵抗的机制,揭示卵巢癌免疫微环境与炎症相关基因之间的关系。不同的R包用于差异基因分析、富集分析、共表达网络构建和预后模型构建。结果:发现卵巢癌患者的预后与炎症相关的多组基因密切相关。免疫浸润微环境、临床病理特征和生存率在使用聚类和免疫微环境分析确定的两种炎症基因表达模式之间存在显著差异。进一步分析发现,高危组m2型巨噬细胞浸润丰度更高,抗肿瘤免疫反应更活跃,肿瘤干性评分更高,预后可能更差,对多种化疗药物和免疫检查点抑制剂的应答率更低。结论:本研究结果为卵巢癌免疫治疗和预后评价提供了新的视角和潜在靶点,为临床治疗和患者管理提供了新的策略和方向。本研究为进一步了解药物反应机制和肿瘤免疫治疗提供了重要信息。它为卵巢癌的治疗和预后改善提供了新的策略和方法。
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来源期刊
Frontiers in Pharmacology
Frontiers in Pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
7.80
自引率
8.90%
发文量
5163
审稿时长
14 weeks
期刊介绍: Frontiers in Pharmacology is a leading journal in its field, publishing rigorously peer-reviewed research across disciplines, including basic and clinical pharmacology, medicinal chemistry, pharmacy and toxicology. Field Chief Editor Heike Wulff at UC Davis is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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