卵巢癌三种亚型的鉴定及基于免疫相关基因的预后模型的构建。
Identification of three subtypes of ovarian cancer and construction of prognostic models based on immune-related genes.
发表日期:2024 Oct 21
作者:
Wen Gao, Hui Yuan, Sheng Yin, Renfang Deng, Zhaodong Ji
来源:
Genes & Diseases
摘要:
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往往限制免疫治疗干预的疗效。因此,有必要描述新的免疫亚型以开发有效的免疫治疗策略。通过共识聚类分析鉴定了OC的免疫亚型。分析亚型之间临床特征、基因突变、mRNA 干性(mRNAsi)和免疫微环境的差异。随后,利用加权相关网络分析,基于免疫亚型的差异表达基因(DEG)构建预后风险模型。将OC患者分为三种具有不同生存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荷、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观察到免疫亚型之间存在显着差异。预后风险模型经过验证,因为独立的预后因素对 OC 患者的生存表现出良好的预测性能。在这项研究中,根据与疫苗反应相关的基因集确定了三种不同的免疫亚型,其中 C2 亚型的预后明显较差。虽然三种亚型的肿瘤突变负荷 (TMB) 没有观察到统计学上的显着差异,但与其他亚型相比,C2 组的同源重组缺陷 (HRD) 评分和 mRNA 干性指数 (mRNAsi) 显着升高。免疫浸润分析表明,C2 亚型可能存在更多的调节性 T (Treg) 细胞,可能有助于对涉及 PARP 抑制剂和免疫疗法的联合疗法产生更有利的反应。这些发现为卵巢癌患者定制免疫治疗提供了一种精准医学方法。此外,C3 亚型的免疫检查点基因表达水平显着降低,这种模式经过独立数据集验证,并且与更好的预后相关。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。© 2024。作者。
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.© 2024. The Author(s).