PMID- 34165261 OWN - NLM STAT- MEDLINE DCOM- 20220214 LR - 20220214 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 10 IP - 15 DP - 2021 Aug TI - Integrative analysis of immune molecular subtypes and microenvironment characteristics of bladder cancer. PG - 5375-5391 LID - 10.1002/cam4.4071 [doi] AB - The emergence of immunotherapy has provided an option of treatment methods for bladder cancer (BC). However, the beneficiaries of immunotherapy are still limited to small-scale patients, and immunotherapy-related adverse events often occur. It is a major challenge for clinical work to study the immune subtypes of BC and the molecular mechanism of immune escape, and identify the immune responders accurately. Here, we explore the immune molecular subtypes of bladder cancer and potential escape mechanisms. First, we screened the expression profiles of 303 differentially expressed immune-related genes in BC patients from the Cancer Genome Atlas (TCGA) database, and successfully identified 4 molecular subtypes of BC. By comparing the clinical characteristics, immune cells infiltration, the expression of checkpoint genes, human leukocyte antigen (HLA) genes, and gene mutation status of different subtypes, we identified different clinical and immunological characteristics of 4 subtypes. Among 4 subtypes, Cluster 2 met the general characteristics of immunotherapy responders and responded well to immunotherapy, while Cluster 4 had the highest expression of immune characteristics, and is similar to the immune environment of normal bladder tissue. Then, the weighted gene co-expression network analysis (WGCNA) of immune-related genes revealed that brown module was positively correlated with subtypes. Pathway enrichment analysis explored the major pathways associated with subtypes, which are also associated with immune escape mechanisms. Moreover, the decision tree model, which was constructed by the principle of random forest screening factors, was also validated in internal validation set and external validation set from the Gene Expression Omnibus (GEO) cohort (GSE133624), and could achieve accurate subtypes prediction for BC patients with high-throughput sequencing. Taken together, we explored the immune molecular subtypes and their mechanisms of BC, and these results may provide guidance for the development of new BC immunotherapy strategies. CI - (c) 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Cao, Jinlong AU - Cao J AUID- ORCID: 0000-0002-6703-8949 AD - Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, People's Republic of China. AD - Key Laboratory of Urological Diseases of Gansu provincial, Lanzhou, People's Republic of China. FAU - Li, Jianpeng AU - Li J AUID- ORCID: 0000-0002-0660-7802 AD - Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, People's Republic of China. AD - Key Laboratory of Urological Diseases of Gansu provincial, Lanzhou, People's Republic of China. FAU - Yang, Xin AU - Yang X AD - Reproductive Medicine Center, The Second Hospital of Lanzhou University, Lanzhou, People's Republic of China. FAU - Li, Pan AU - Li P AD - Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, People's Republic of China. AD - Key Laboratory of Urological Diseases of Gansu provincial, Lanzhou, People's Republic of China. FAU - Yao, Zhiqiang AU - Yao Z AUID- ORCID: 0000-0002-4633-7624 AD - Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, People's Republic of China. AD - Key Laboratory of Urological Diseases of Gansu provincial, Lanzhou, People's Republic of China. FAU - Han, Dali AU - Han D AD - Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, People's Republic of China. AD - Key Laboratory of Urological Diseases of Gansu provincial, Lanzhou, People's Republic of China. FAU - Ying, Lijun AU - Ying L AD - Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, People's Republic of China. AD - Key Laboratory of Urological Diseases of Gansu provincial, Lanzhou, People's Republic of China. FAU - Wang, Lijie AU - Wang L AD - Department of Gynecology, The Second Hospital of Lanzhou University, Lanzhou, People's Republic of China. FAU - Tian, Junqiang AU - Tian J AUID- ORCID: 0000-0002-4529-4650 AD - Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, People's Republic of China. AD - Key Laboratory of Urological Diseases of Gansu provincial, Lanzhou, People's Republic of China. LA - eng GR - 561219007/the Fundamental Research Funds for the Central Universities/ GR - CY2017-BJ16/Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital/ GR - GWGL2013-30/Industry Planning Project of Health Department of Gansu Province/ GR - 201704/Cuiying Graduate Supervisor Applicant Training Program of Lanzhou University Second Hospital/ GR - ynbskyjj2015-2-7/Doctoral Research Foundation of Lanzhou University Second Hospital/ GR - 2017KJGG0052/Science and Technology Project of Chengguan District, Lanzhou City, Gansu Province Science and Technology Bureau/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210624 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (HLA Antigens) SB - IM MH - Databases, Genetic MH - Decision Trees MH - Gene Expression Profiling MH - Genes, cdc MH - HLA Antigens/genetics MH - Humans MH - Immunity, Cellular MH - *Immunotherapy/adverse effects MH - Mutation MH - Reproducibility of Results MH - Treatment Outcome MH - Tumor Escape/genetics/*immunology MH - Urinary Bladder/immunology MH - Urinary Bladder Neoplasms/genetics/*immunology/*therapy PMC - PMC8335815 OTO - NOTNLM OT - decision tree model OT - immune molecular subtypes OT - immunotherapy OT - random forest OT - the cancer genome atlas COIS- The authors declare no financial conflict of interest. EDAT- 2021/06/25 06:00 MHDA- 2022/02/15 06:00 PMCR- 2021/06/24 CRDT- 2021/06/24 09:42 PHST- 2021/05/26 00:00 [revised] PHST- 2020/11/11 00:00 [received] PHST- 2021/06/01 00:00 [accepted] PHST- 2021/06/25 06:00 [pubmed] PHST- 2022/02/15 06:00 [medline] PHST- 2021/06/24 09:42 [entrez] PHST- 2021/06/24 00:00 [pmc-release] AID - CAM44071 [pii] AID - 10.1002/cam4.4071 [doi] PST - ppublish SO - Cancer Med. 2021 Aug;10(15):5375-5391. doi: 10.1002/cam4.4071. Epub 2021 Jun 24.