单样本基因集富集分析揭示了卵巢癌中免疫相关基因的临床意义。
Single-sample gene set enrichment analysis reveals the clinical implications of immune-related genes in ovarian cancer.
发表日期:2024
作者:
Weiwei Gong, Mingqin Kuang, Hongxi Chen, Yiheng Luo, Keli You, Bin Zhang, Yueyang Liu
来源:
GENES & DEVELOPMENT
摘要:
卵巢癌(OC)是一种常见的妇科恶性肿瘤,预后差,肿瘤异质性大。由于卵巢癌复杂的肿瘤免疫微环境(TIME),只有少数患者对免疫治疗有免疫反应。为了研究免疫功能的差异并识别 OC 中潜在的生物标志物,我们建立了一个具有免疫相关基因 (IRG) 差异表达的预后风险评分模型 (PRSM),以识别关键的预后 IRG 特征。单样本基因集富集分析 ( ssGSEA)用于调查 372 名 OC 患者体内各种免疫细胞的浸润情况。然后利用COX回归分析和Lasso回归分析筛选IRG并构建PRSM。接下来,评估不同风险组对免疫检查点表达和肿瘤突变负荷的免疫治疗敏感性。最后,创建列线图来指导患者预后的临床评估。在这项研究中,鉴定了 320 个免疫相关基因 (IRG),其中 13 个被选择性纳入预后风险评分模型 (PRSM)。该模型显示,与低风险组相比,高风险组患者的预后较差,免疫检查点表达较低,肿瘤突变负荷水平较低。基于风险评分的列线图可以区分 OC 患者的风险亚型和个体预后。此外,M1巨噬细胞可能是OC患者免疫治疗的关键靶点。通过深入分析OC的免疫微环境,构建PRSM来预测OC患者的预后,并确定从免疫治疗中受益的患者亚组。版权© 2024 龚、匡、陈、罗、游、张、刘。
Ovarian cancer (OC) is a common gynecological malignancy with poor prognosis and substantial tumor heterogeneity. Due to the complex tumor immune microenvironment (TIME) among ovarian cancer, only a few patients have an immune response to immunotherapy. To investigate the differences in immune function and identify potential biomarkers in OC, we established a prognostic risk scoring model (PRSM) with differential expression of immune-related genes (IRGs) to identify critical prognostic IRG signatures.Single-sample gene set enrichment analysis (ssGSEA) was used to investigate the infiltration of various immune cells in 372 OC patients. Then, COX regression analysis and Lasso regression analysis were used to screen IRGs and construct PRSM. Next, the immunotherapy sensitivity of different risk groups regarding the immune checkpoint expression and tumor mutation burden was evaluated. Finally, a nomogram was created to guide the clinical evaluation of the patient prognosis.In this study, 320 immune-related genes (IRGs) were identified, 13 of which were selectively incorporated into a Prognostic Risk Scoring Model (PRSM). This model revealed that the patients in the high-risk group were characterized as having poorer prognosis, lower expression of immune checkpoints, and decreased tumor mutation load levels compared with those in the low-risk group. The nomogram based on the risk score can distinguish the risk subtypes and individual prognosis of patients with OC. Additionally, M1 macrophages may be the critical target for immunotherapy in OC patients.With the in-depth analysis of the immune microenvironment of OC, the PRSM was constructed to predict the OC patient prognosis and identify the subgroup of the patients benefiting from immunotherapy.Copyright © 2024 Gong, Kuang, Chen, Luo, You, Zhang and Liu.