Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
Front Immunol. 2021 Nov 22;12:763791. doi: 10.3389/fimmu.2021.763791. eCollection 2021.
Ovarian cancer (OC) is a devastating malignancy with a poor prognosis. The complex tumor immune microenvironment results in only a small number of patients benefiting from immunotherapy. To explore the different factors that lead to immune invasion and determine prognosis and response to immune checkpoint inhibitors (ICIs), we established a prognostic risk scoring model (PRSM) with differential expression of immune-related genes (IRGs) to identify key prognostic IRGs. Patients were divided into high-risk and low-risk groups according to their immune and stromal scores. We used a bioinformatics method to identify four key IRGs that had differences in expression between the two groups and affected prognosis. We evaluated the sensitivity of treatment from three aspects, namely chemotherapy, targeted inhibitors (TIs), and immunotherapy, to evaluate the value of prediction models and key prognostic IRGs in the clinical treatment of OC. Univariate and multivariate Cox regression analyses revealed that these four key IRGs were independent prognostic factors of overall survival in OC patients. In the high-risk group comprising four genes, macrophage M0 cells, macrophage M2 cells, and regulatory T cells, observed to be associated with poor overall survival in our study, were higher. The high-risk group had a high immunophenoscore, indicating a better response to ICIs. Taken together, we constructed a PRSM and identified four key prognostic IRGs for predicting survival and response to ICIs. Finally, the expression of these key genes in OC was evaluated using RT-qPCR. Thus, these genes provide a novel predictive biomarker for immunotherapy and immunomodulation.
卵巢癌 (OC) 是一种预后不良的恶性肿瘤。复杂的肿瘤免疫微环境导致只有少数患者受益于免疫疗法。为了探索导致免疫浸润的不同因素,并确定预后和对免疫检查点抑制剂 (ICI) 的反应,我们建立了一个具有免疫相关基因 (IRGs) 差异表达的预后风险评分模型 (PRSM),以确定关键的预后 IRGs。根据免疫和基质评分,患者被分为高风险组和低风险组。我们使用生物信息学方法来识别两组之间表达差异并影响预后的四个关键 IRGs。我们从化疗、靶向抑制剂 (TIs) 和免疫治疗三个方面评估了治疗的敏感性,以评估预测模型和关键预后 IRGs 在 OC 临床治疗中的价值。单因素和多因素 Cox 回归分析表明,这四个关键 IRGs 是 OC 患者总生存的独立预后因素。在包含四个基因的高风险组中,我们观察到巨噬细胞 M0 细胞、巨噬细胞 M2 细胞和调节性 T 细胞与较差的总生存相关。高风险组具有较高的免疫表型评分,表明对 ICI 的反应更好。总之,我们构建了一个 PRSM,并确定了四个关键的预后 IRGs 来预测生存和对 ICI 的反应。最后,使用 RT-qPCR 评估了这些关键基因在 OC 中的表达。因此,这些基因为免疫治疗和免疫调节提供了一种新的预测生物标志物。