识别卵巢癌的三种亚型及基于免疫相关基因的预后模型构建

免疫治疗已革新卵巢癌（OC）的治疗，但不同的免疫微环境常限制免疫干预的疗效。因此，亟需划定新的免疫亚型，以开发有效的免疫治疗策略。采用一致性聚类分析（consensus cluster analysis）识别OC的免疫亚型。分析亚型之间的临床特征、基因突变、mRNA的干性（mRNAsi）和免疫微环境的差异。随后，利用加权相关网络分析（WGCNA）基于免疫亚型的差异表达基因（DEGs）构建预后风险模型。结果显示，OC患者被分为三种具有不同存活率和临床特征的免疫亚型。不同亚型表现出不同的肿瘤突变负担、同源重组缺陷（HRD）和mRNAsi水平。免疫检查点表达和免疫原性细胞死亡（ICD）在免疫亚型间差异显著。预后风险模型作为独立预后因素，具有良好的生存预测能力。在本研究中，基于疫苗反应相关基因集，鉴定出三种免疫亚型，其中C2亚型预后明显较差。虽然三亚型间肿瘤突变负担（TMB）没有统计学差异，但C2组的同源重组缺陷（HRD）评分和mRNA干性指数（mRNAsi）显著升高。免疫浸润分析显示，C2亚型可能具有较多的调节性T（Treg）细胞，可能有助于对PARP抑制剂和免疫治疗联合疗法的更好反应。这些发现为卵巢癌患者的精准免疫治疗提供了依据。此外，C3亚型免疫检查点基因表达显著较低，经独立数据集验证，与更佳预后相关。进一步研究发现，免疫相关基因FCRL5与卵巢癌预后相关，体外实验显示其影响卵巢癌细胞系SKOV3的增殖和迁移。

Immunotherapy has revolutionized the treatment of ovarian cancer (OC), but different immune microenvironments often constrain the efficacy of immunotherapeutic interventions. Therefore, there is an imperative to delineate novel immune subtypes for development of efficacious immunotherapeutic strategies.The immune subtypes of OC were identified by consensus cluster analysis. The differences in clinical features, genetic mutations, mRNA stemness (mRNAsi) and immune microenvironments were analyzed among subtypes. Subsequently, prognostic risk models were constructed based on differentially expressed genes (DEGs) of the immune subtypes using weighted correlation network analysis.OC patients were classified into three immune subtypes with distinct survival rates and clinical features. Different subtypes exhibited varying tumor mutation burdens, homologous recombination deficiencies, and mRNAsi levels. Significant differences were observed among immune subtypes in terms of immune checkpoint expression and immunogenic cell death. Prognostic risk models were validated as independent prognostic factors demonstrated great predictive performance for survival of OC patients.In this study, three distinct immune subtypes were identified based on gene sets related to vaccine response, with the C2 subtype exhibiting significantly worse prognosis. While no statistically significant differences in tumor mutation burden (TMB) were observed across the three subtypes, the homologous recombination deficiency (HRD) score and mRNA stemness index (mRNAsi) were notably elevated in the C2 group compared to the others. Immune infiltration analysis indicated that the C2 subtype may have an increased presence of regulatory T (Treg) cells, potentially contributing to a more favorable response to combination therapies involving PARP inhibitors and immunotherapy. These findings offer a precision medicine approach for tailoring immunotherapy in ovarian cancer patients. Moreover, the C3 subtype demonstrated significantly lower expression levels of immune checkpoint genes, a pattern validated by independent datasets, and associated with a better prognosis. Further investigation revealed that the immune-related gene FCRL5 correlates with ovarian cancer prognosis, with in vitro experiments showing that it influences the proliferation and migration of the ovarian cancer cell line SKOV3.