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Ferroptosis Patterns and Tumor Microenvironment Infiltration Characterization in Bladder Cancer

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单位: [1]Huazhong Univ Sci & Technol,Tongji Hosp,Dept & Inst Urol,Tongji Med Coll,Wuhan,Peoples R China
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关键词: ferroptosis tumor microenvironment tumor mutation burden bladder cancer immunotherapy

摘要:
Background: Ferroptosis is a unique iron-dependent form of cell death and bladder cancer (BCa) is one of the top ten most common cancer types in the world. However, the role of ferroptosis in shaping the tumor microenvironment and influencing tumor clinicopathological features remains unknown.Methods: Using the data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we comprehensively evaluated the ferroptosis patterns of 570 BCa samples based on 234 validated ferroptosis genes reported in the FerrDb database and systematically correlated these ferroptosis patterns with tumor microenvironment (TME) cell-infiltrating characteristics. The ferroptosis score was constructed to quantify ferroptosis patterns of individuals using principal component analysis (PCA) algorithms.Results: Four distinct ferroptosis patterns and two gene clusters were finally determined. Significant differences in clinical characteristics and the prognosis of patients were found among different ferroptosis patterns and gene clusters, so were in the mRNA transcriptome and the landscape of TME immune cell infiltration. We also established a set of scoring system to quantify the ferroptosis pattern of individual patients with BCa named the ferroptosis score, which was discovered to tightly interact with clinical signatures such as the TNM category and tumor grade and could predict the prognosis of patients with BCa. Moreover, tumor mutation burden (TMB) was positively correlated to the ferroptosis score, and the low ferroptosis score was related to a better response to immunotherapy using PD-1 blockade. Finally, we also found there existed a positive correlation between the sensitivity to cisplatin chemotherapy and ferroptosis score.Conclusions: Our work demonstrated and interpreted the complicated regulation mechanisms of ferroptosis on the tumor microenvironment and that better understanding and evaluating ferroptosis patterns could be helpful in guiding the clinical therapeutic strategy and improving the prognosis of patients with BCa.

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出版当年[2021]版:
大类 | 3 区 生物学
小类 | 2 区 发育生物学 3 区 细胞生物学
最新[2025]版:
大类 | 2 区 生物学
小类 | 2 区 发育生物学 3 区 细胞生物学
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出版当年[2020]版:
Q1 DEVELOPMENTAL BIOLOGY Q2 CELL BIOLOGY
最新[2023]版:
Q1 DEVELOPMENTAL BIOLOGY Q2 CELL BIOLOGY

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第一作者单位: [1]Huazhong Univ Sci & Technol,Tongji Hosp,Dept & Inst Urol,Tongji Med Coll,Wuhan,Peoples R China
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