Table_1_Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer.docx

Predictive models could indicate the clinical outcome of patients with carcinoma. Cervical cancer is one of the most frequently diagnosed female malignancies. Herein, we proposed an immune infiltration-related gene signature that predicts prognosis of patients with cervical cancer and depicts the immune landscape as well. We utilized the transcriptome data of The Cancer Genome Atlas (TCGA) and estimated the infiltration level of 28 immune cell types. We screened out four immune cell types conducive to patient survival and recognized their shared differentially expressed genes (DEGs). Four core genes (CHIT1, GTSF1L, PLA2G2D, and GNG8) that composed the ultimate signature were identified via univariate and multivariate Cox regression. The optimal model we built up could distinguish patients with cervical cancer into high-score and low-score subgroups. These two subgroups showed disparity in aspects of patient survival, immune infiltration landscape, and response to immune checkpoint inhibitors. Additionally, we found that GTSF1L was decreased gradually along with the severity of cervical lesions, and its potential role in immune contexture and clinical practice were also demonstrated. Our results suggested that the Immunoscore based on four immune-related genes could serve as a supplementary criterion to effectively foresee the survival outcome, tumor infiltration status, and immunotherapy efficacy of cervical cancer patients.

预测模型可用于研判癌症患者的临床结局。宫颈癌是最常见的女性恶性肿瘤之一。本研究构建了一种与免疫浸润相关的基因标记物，既可预测宫颈癌患者的预后，亦可揭示其免疫微环境全貌。本研究使用癌症基因组图谱（The Cancer Genome Atlas, TCGA）的转录组数据，对28种免疫细胞的浸润水平进行了量化评估。本研究筛选出4种与患者良好生存相关的免疫细胞类型，并鉴定出它们共有的差异表达基因（differentially expressed genes, DEGs）。通过单因素及多因素Cox回归分析，本研究最终确定了4个核心基因（CHIT1、GTSF1L、PLA2G2D及GNG8）以构建该基因标记物。所构建的最优模型可将宫颈癌患者划分为高评分亚组与低评分亚组。这两个亚组在患者生存状况、免疫浸润特征以及免疫检查点抑制剂治疗应答方面均存在显著差异。此外，本研究发现GTSF1L的表达水平随宫颈病变程度加重呈逐渐降低趋势，并阐明了其在免疫微环境及临床实践中的潜在作用。本研究结果表明，基于4个免疫相关基因的免疫评分（Immunoscore）可作为补充评估指标，有效预测宫颈癌患者的生存结局、肿瘤浸润状态及免疫治疗疗效。