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一种用于黑色素瘤预后的免疫相关基因特征的开发

Development of an Immune-Related Gene Signature for Prognosis in Melanoma.

作者信息

Zhang Jia-An, Zhou Xu-Yue, Huang Dan, Luan Chao, Gu Heng, Ju Mei, Chen Kun

机构信息

Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, China.

出版信息

Front Oncol. 2021 Jan 21;10:602555. doi: 10.3389/fonc.2020.602555. eCollection 2020.

Abstract

Melanoma remains a potentially deadly malignant tumor. The incidence of melanoma continues to rise. Immunotherapy has become a new treatment method and is widely used in a variety of tumors. Original melanoma data were downloaded from TCGA. ssGSEA was performed to classify them. GSVA software and the "hclust" package were used to analyze the data. The ESTIMATE algorithm screened DEGs. The edgeR package and Venn diagram identified valid immune-related genes. Univariate, LASSO and multivariate analyses were used to explore the hub genes. The "rms" package established the nomogram and calibrated the curve. Immune infiltration data were obtained from the TIMER database. Compared with that of samples in the high immune cell infiltration cluster, we found that the tumor purity of samples in the low immune cell infiltration cluster was higher. The immune score, ESTIMATE score and stromal score in the low immune cell infiltration cluster were lower. In the high immune cell infiltration cluster, the immune components were more abundant, while the tumor purity was lower. The expression levels of TIGIT, PDCD1, LAG3, HAVCR2, CTLA4 and the HLA family were also higher in the high immune cell infiltration cluster. Survival analysis showed that patients in the high immune cell infiltration cluster had shorter OS than patients in the low immune cell infiltration cluster. IGHV1-18, CXCL11, LTF, and HLA-DQB1 were identified as immune cell infiltration-related DEGs. The prognosis of melanoma was significantly negatively correlated with the infiltration of CD4+ T cells, CD8+ T cells, dendritic cells, neutrophils and macrophages. In this study, we identified immune-related melanoma core genes and relevant immune cell subtypes, which may be used in targeted therapy and immunotherapy of melanoma.

摘要

黑色素瘤仍然是一种具有潜在致命性的恶性肿瘤。黑色素瘤的发病率持续上升。免疫疗法已成为一种新的治疗方法,并广泛应用于多种肿瘤。从TCGA下载原始黑色素瘤数据。进行单样本基因集富集分析(ssGSEA)对其进行分类。使用基因集变异分析(GSVA)软件和“hclust”包来分析数据。ESTIMATE算法筛选差异表达基因(DEGs)。edgeR包和韦恩图确定有效的免疫相关基因。采用单因素、套索和多因素分析来探索核心基因。“rms”包建立列线图并校准曲线。免疫浸润数据从TIMER数据库获得。与高免疫细胞浸润簇中的样本相比,我们发现低免疫细胞浸润簇中样本的肿瘤纯度更高。低免疫细胞浸润簇中的免疫评分、ESTIMATE评分和基质评分更低。在高免疫细胞浸润簇中,免疫成分更丰富,而肿瘤纯度更低。高免疫细胞浸润簇中TIGIT、程序性死亡蛋白1(PDCD1)、淋巴细胞激活基因3(LAG3)、甲型肝炎病毒细胞受体2(HAVCR2)、细胞毒性T淋巴细胞相关蛋白4(CTLA4)和人类白细胞抗原(HLA)家族的表达水平也更高。生存分析表明,高免疫细胞浸润簇中的患者总生存期(OS)比低免疫细胞浸润簇中的患者短。免疫球蛋白重链可变区1-18(IGHV1-18)、CXC趋化因子配体11(CXCL11)、乳铁蛋白(LTF)和HLA-DQB1被鉴定为免疫细胞浸润相关的差异表达基因。黑色素瘤的预后与CD4+T细胞、CD8+T细胞、树突状细胞、中性粒细胞和巨噬细胞的浸润显著负相关。在本研究中,我们鉴定了免疫相关的黑色素瘤核心基因和相关免疫细胞亚型,这可能用于黑色素瘤的靶向治疗和免疫治疗。

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