Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Immunol. 2021 Oct 20;12:751594. doi: 10.3389/fimmu.2021.751594. eCollection 2021.
Ovarian cancer (OC) is an immunogenetic disease that contains tumor-infiltrating lymphocytes (TILs), and immunotherapy has become a novel treatment for OC. With the development of next-generation sequencing (NGS), profiles of gene expression and comprehensive landscape of immune cells can be applied to predict clinical outcome and response to immunotherapy.
We obtained data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and applied two computational algorithms (CIBERSORT and ESTIMATE) for consensus clustering of immune cells. Patients were divided into two subtypes using immune cell infiltration (ICI) levels. Then, differentially expressed genes (DEGs) associated with immune cell infiltration (ICI) level were identified. We also constructed ICI score after principle-component analysis (PCA) for dimension reduction.
Patients in ICI cluster B had better survival than those in ICI cluster A. After construction of ICI score, we found that high ICI score had better clinical OS and significantly higher tumor mutation burden (TMB). According to the expression of immune checkpoints, the results showed that patients in high ICI group showed high expression of CTLA4, PD1, PD-L1, and PD-L2, which implies that they might benefit from immunotherapy. Besides, patients in high ICI group showed higher sensitivity to two first-line chemotherapy drugs (Paclitaxel and Cisplatin).
ICI score is an effective prognosis-related biomarker for OC and can provide valuable information on the potential response to immunotherapy.
卵巢癌(OC)是一种免疫遗传疾病,包含肿瘤浸润淋巴细胞(TILs),免疫疗法已成为 OC 的一种新治疗方法。随着下一代测序(NGS)的发展,可以应用基因表达谱和免疫细胞综合图谱来预测临床结果和对免疫疗法的反应。
我们从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中获取数据,并应用两种计算算法(CIBERSORT 和 ESTIMATE)对免疫细胞进行共识聚类。根据免疫细胞浸润(ICI)水平将患者分为两个亚型。然后,鉴定与免疫细胞浸润(ICI)水平相关的差异表达基因(DEGs)。我们还通过主成分分析(PCA)构建 ICI 评分以进行降维。
ICI 聚类 B 中的患者比 ICI 聚类 A 中的患者具有更好的生存。构建 ICI 评分后,我们发现高 ICI 评分具有更好的临床 OS 和显著更高的肿瘤突变负担(TMB)。根据免疫检查点的表达,结果表明高 ICI 组的患者 CTLA4、PD1、PD-L1 和 PD-L2 的表达较高,这意味着他们可能受益于免疫疗法。此外,高 ICI 组的患者对两种一线化疗药物(紫杉醇和顺铂)表现出更高的敏感性。
ICI 评分是 OC 的一种有效的预后相关生物标志物,可提供有关免疫治疗潜在反应的有价值信息。