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肿瘤突变负荷与免疫浸润在宫颈鳞状细胞癌中的预后价值

Prognostic Value of Tumor Mutational Burden Related to Immune Infiltration in Cervical Squamous Cell Carcinoma.

作者信息

Wen Fang, Ruan Shuai, Huang Wenjie, Chen Xiaoxue, Wang Yulan, Gu Suping, Liu Jiatong, Liu Shenlin, Shu Peng

机构信息

Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.

出版信息

Front Med (Lausanne). 2021 Nov 11;8:755657. doi: 10.3389/fmed.2021.755657. eCollection 2021.

Abstract

Cervical squamous cell carcinoma is one of the most common causes of female cancer deaths worldwide. At present, immunotherapy using immune checkpoint blockade (ICB) has improved the prognosis of many cancer patients, and neoantigens generated by mutations may serve as potential biomarkers for predicting the outcome of ICB therapy. In this study, we identified missense mutations as the most frequent in landscapes of gene mutation in cervical squamous cell carcinoma (CESC) samples. Patients with higher tumor mutation burden (TMB) presented higher overall survival (OS). In addition, there was a significant correlation between the high TMB group and fractions of most immune cells. Univariate and multivariate Cox regression analyses identified five hub genes (IFNG, SERPINA3, CCL4L2, TNFSF15, and IL1R1) that were used to build a prognostic model. In the prognostic model, the low-risk group achieved better OS. Mutations in the five hub genes mainly affected the infiltration level of CD8+ T cells and dendritic cells. In conclusion, our study is valuable for exploring the role of TMB and its relationship with immune infiltration in CESC. Moreover, the prognosis model may help predict the sensitivity of patients to immunotherapy and provide underlying biomarkers for personalized immunotherapy.

摘要

宫颈鳞状细胞癌是全球女性癌症死亡的最常见原因之一。目前,使用免疫检查点阻断(ICB)的免疫疗法改善了许多癌症患者的预后,由突变产生的新抗原可能作为预测ICB治疗结果的潜在生物标志物。在本研究中,我们确定错义突变是宫颈鳞状细胞癌(CESC)样本基因突变图谱中最常见的类型。肿瘤突变负荷(TMB)较高的患者总生存期(OS)更长。此外,高TMB组与大多数免疫细胞比例之间存在显著相关性。单因素和多因素Cox回归分析确定了五个核心基因(IFNG、SERPINA3、CCL4L2、TNFSF15和IL1R1),并用于构建预后模型。在该预后模型中,低风险组的总生存期更佳。五个核心基因中的突变主要影响CD8+T细胞和树突状细胞的浸润水平。总之,我们的研究对于探索TMB在CESC中的作用及其与免疫浸润的关系具有重要价值。此外,该预后模型可能有助于预测患者对免疫治疗的敏感性,并为个性化免疫治疗提供潜在的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3b/8631969/c0e895e0ee38/fmed-08-755657-g0001.jpg

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