鉴定卵巢癌的三种亚型和基于免疫相关基因的预后模型的构建

免疫疗法彻底改变了卵巢癌（OC）的治疗，但不同的免疫微环境通常会限制免疫治疗干预措施的疗效。因此，必须描绘出新型免疫亚型以开发有效的免疫治疗策略。OC的免疫亚型通过共识群集分析鉴定出来。在亚型之间分析了临床特征，基因突变，mRNASI（mRNASI）和免疫微环境的差异。随后，使用加权相关网络分析基于免疫亚型的差异表达基因（DEG）构建了预后风险模型。COC患者被分为三种具有不同存活率和临床特征的免疫亚型。不同的亚型表现出不同的肿瘤突变负担，同源重组缺陷和mRNASI水平。在免疫检查点表达和免疫原性细胞死亡方面，免疫亚型之间观察到显着差异。预后风险模型被证实是因为独立的预后因素证明了OC患者存活的出色预测性能。在这项研究中，基于与疫苗反应相关的基因集鉴定出三种不同的免疫亚型，C2亚型的预后明显较差。尽管在三个亚型中未观察到肿瘤突变负担（TMB）的统计学显着差异，但与其他相比，C2组的同源重组缺乏（HRD）得分（HRD）得分（HRD）得分（MRNASI）显着升高。免疫浸润分析表明，C2亚型可能存在调节t（TREG）细胞的存在增加，这有可能导致对涉及PARP抑制剂和免疫疗法的组合疗法的更有利反应。这些发现为卵巢癌患者调整免疫疗法提供了一种精确的医学方法。此外，C3亚型表现出明显较低的免疫检查点基因表达水平，该模式通过独立数据集验证，并且与更好的预后相关。进一步的研究表明，与免疫相关的基因FCRL5与卵巢癌的预后相关，体外实验表明它影响了卵巢癌细胞系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.