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Identification and Quantification of Iron Metabolism Landscape on Therapy and Prognosis in Bladder Cancer

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单位: [1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Urol,Wuhan,Peoples R China [2]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Geriatr,Wuhan,Peoples R China
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关键词: bladder cancer iron metabolism tumor microenvionment prognostic signature nomogram bioinformactics

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The morbidity of bladder cancer (BLCA) is high and has gradually elevated in recent years. BLCA is also characterized by high recurrence and high invasiveness. Due to the drug resistance and lack of effective prognostic indicators, the prognosis of patients with BLCA is greatly affected. Iron metabolism is considered to be a pivot of tumor occurrence, progression, and tumor microenvironment (TME) in tumors, but there is little research in BLCA. Herein, we used univariate COX regression analysis to screen 95 prognosis-related iron metabolism-related genes (IMRGs) according to transcription RNA sequencing and prognosis information of the Cancer Genome Atlas (TCGA) database. TCGA-BLCA cohort was clustered into four distinct iron metabolism patterns (C1, C2, C3, and C4) by the non-negative matrix factorization (NMF) algorithm. Survival analysis showed that C1 and C3 patterns had a better prognosis. Gene set variant analysis (GSVA) revealed that C2 and C4 patterns were mostly enriched in carcinogenic and immune activation pathways. ESTIMATE and single sample gene set enrichment analysis (ssGSEA) also confirmed the level of immune cell infiltration in C2 and C4 patterns was significantly elevated. Moreover, the immune checkpoint genes in C2 and C4 patterns were observably overexpressed. Studies on somatic mutations showed that the tumor mutation burden (TMB) of C1 and C4 patterns was the lowest. Chemotherapy response assessment revealed that C2 pattern was the most sensitive to chemotherapy, while C3 pattern was the most insensitive. Then we established the IMRG prognosis signature (IMRGscore) by the least absolute shrinkage and selection operator (LASSO), including 13 IMRGs (TCIRG1, CTSE, ATP6V0A1, CYP2C8, RNF19A, CYP4Z1, YPEL5, PLOD1, BMP6, CAST, SCD, IFNG, and ASIC3). We confirmed IMRGscore could be utilized as an independent prognostic indicator. Therefore, validation and quantification of iron metabolism landscapes will help us comprehend the formation of the BLCA immunosuppressive microenvironment, guide the selection of chemotherapeutic drugs and immunotherapy, and predict the prognosis of patients.

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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,Tongji Med Coll,Dept Urol,Wuhan,Peoples R China
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