Profiles of Immune Infiltration in Bladder Cancer and its Clinical Significance: an Integrative Genomic Analysis
Profiles of Immune Infiltration in Bladder Cancer and its Clinical Significance: an Integrative Genomic Analysis
复制标题
DOI：
10.7150/ijms.42151
复制
发表时间：
2020-01-01
影响因子：
3.6
通讯作者：
Shi, Benkang
中科院分区：
文献类型：
--
作者：
Wu, Zonglong;Zhu, Kejia;Shi, Benkang
肿瘤浸润性免疫细胞与膀胱癌的预后密切相关。肿瘤浸润性免疫细胞的分析通常基于免疫组织化学分析。由于许多免疫细胞标记蛋白对不同的免疫细胞不具有特异性，这可能导致误导或不完整。CIBERSORT是一种利用基因表达数据估计混合细胞群中特定细胞类型的算法。本研究采用CIBERSORT算法对免疫细胞浸润特征进行识别。基因表达谱、突变数据和临床数据来自癌症基因组图谱（TCGA）数据库。采用无监督共识聚类方法，基于22种免疫细胞类型的分数，获得膀胱癌免疫细胞浸润亚型。鉴定出4种具有不同免疫浸润和突变特征的免疫细胞群。此外，这种分层与预后相关，第2类预后最好，第1类最差。这些簇表现出不同的mRNA表达模式。亚型1的特征基因主要参与细胞分裂，亚型2的特征基因主要参与抗原加工和递呈，亚型3的特征基因主要参与表皮细胞分化，亚型4的特征基因主要参与体液免疫应答。这些差异可能影响膀胱癌的发展、对治疗的敏感性以及预后。通过进一步的验证，本研究可能有助于个性化治疗和精准医疗的发展。
Tumor-infiltrating immune cells are closely related to the prognosis of bladder cancer. Analysis of tumor infiltrating immune cells is usually based on immunohistochemical analysis. Since many immune cell marker proteins are not specific for different immune cells, which may induce misleading or incomplete. CIBERSORT is an algorithm to estimate specific cell types in a mixed cell population using gene expression data. In this study, the CIBERSORT algorithm was used to identify the immune cell infiltration signatures. The gene expression profiles, mutation data, and clinical data were collected from The Cancer Genome Atlas (TCGA) database. Unsupervised consensus clustering was used to acquire the immune cell infiltration subtypes of bladder cancer based on the fractions of 22 immune cell types. Four immune cell clusters with different immune infiltrate and mutation characteristics were identified. In addition, this stratification has a prognostic relevance, with cluster 2 having the best outcome, cluster 1 the worst. These clusters showed distinct mRNA expression patterns. The characteristic genes in subtype cluster 1 were mainly involved in cell division, those in subtype cluster 2 were mainly related in antigen processing and presentation, those in subtype cluster 3 were mainly involved in epidermal cell differentiation, and those in subtype cluster 4 were mainly related in the humoral immune response. These differences may affect the development of the bladder cancer, the sensitivity to treatment as well as the prognosis. Through further validation, this study may contribute to the development of personalized therapy and precision medical treatments.