研究表明，衰老显著影响各种肿瘤的发生、生存结果和治疗效果，包括高级别浆液性卵巢癌（HGSOC）。因此，本研究旨在首次构建一个与衰老相关的风险特征，以帮助评估HGSOC患者的免疫原性和生存状态。根据5个独立队列，共获得1727例HGSOC患者的mRNA基因组数据和临床生存数据。采用Lasso-Cox回归模型，识别对预后影响最大的衰老基因。通过整合确定的基因表达和相应的模型权重，开发了风险特征。此外，基于不同的风险亚群，评估了微环境中的免疫细胞、信号通路和免疫相关特征。最后，使用进行免疫检查点抑制剂（ICI）治疗的2个队列，确认了所识别的风险特征对ICI疗效的影响。从相关基因中构建了一个包含12个基因的衰老特征，在发现队列和4个验证队列中低风险HGSOC患者显示了改善的生存结果（所有P<.05）。低风险亚群显示了更好的免疫细胞浸润和免疫通路的富集，以及进一步免疫学分析中的ICI预测因子。值得注意的是，在免疫治疗队列中，观察到低风险的衰老特征与更好的免疫治疗效果和增加的响应率相联系。总之，我们构建的衰老特征不仅有助于评估预后结果和免疫原性，更重要的是有助于评估ICI治疗的疗效。该特征为预后预测和免疫治疗效果评估提供了有价值的见解，最终促进了HGSOC患者的个体化治疗。 © 2023 the Author(s). 由Wolters Kluwer Health, Inc.出版

Studies have shown that aging significantly impacts tumorigenesis, survival outcome, and treatment efficacy in various tumors, covering high-grade serous ovarian cancer (HGSOC). Therefore, the objective for this investigation is to construct an aging-relevant risk signature for the first time, which will help evaluate the immunogenicity and survival status for patients with HGSOC. Totaling 1727 patients with HGSOC, along with their mRNA genomic data and clinical survival data, were obtained based on 5 independent cohorts. The Lasso-Cox regression model was utilized to identify the aging genes that had the most significant impact on prognosis. The risk signature was developed by integrating the determined gene expression and accordant model weights. Additionally, immunocytes in the microenvironment, signaling pathways, and immune-relevant signatures were assessed based on distinct risk subgroups. Finally, 2 cohorts that underwent treatment with immune checkpoint inhibitor (ICI) were employed to confirm the effects of identified risk signature on ICI efficacy. An aging signature was constructed from 12 relevant genes, which showed improved survival outcomes in low-risk HGSOC patients across discovery and 4 validation cohorts (all P < .05). The low-risk subgroup showed better immunocyte infiltration and higher enrichment of immune pathways and ICI predictors based on further immunology analysis. Notably, in the immunotherapeutic cohorts, low-risk aging signature was observed to link to better immunotherapeutic outcomes and increased response rates. Together, our constructed signature of aging has the potential to assess not only the prognosis outcome and immunogenicity, but also, importantly, the efficacy of ICI treatment. This signature provides valuable insights for prognosis prediction and immunotherapeutic effect evaluation, ultimately promoting individualized treatment for HGSOC patients.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.