Defining muscle-invasive bladder cancer immunotypes by introducing tumor mutation burden, CD8+ T cells, and molecular subtypes
| Autor: | Irina A. Tuzankina, Mikhail A. Bolkov, Guoqing Liu, Guojun Liu, Zihao Chen, Valery A. Chereshnev, Khyber Shinwari, Zhifeng Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_treatment
CELL INFILTRATION CD8-Positive T-Lymphocytes medicine.disease_cause CD8+ T LYMPHOCYTE 0302 clinical medicine HUMAN CELL Cytotoxic T cell CANCER IMMUNOTHERAPY IMMUNOTYPE CD8+ T CELLS TGF BETA SIGNALING 0303 health sciences Mutation biology GENE ONTOLOGY PI3K/AKT SIGNALING Muscles HUMAN General Medicine Phenotype 030220 oncology & carcinogenesis Immunotherapy ACTA2 CANCER SURVIVAL Signal Transduction GENE EXPRESSION Immunotype lcsh:QH426-470 PHOSPHATIDYLINOSITOL 3 KINASE CANCER CLASSIFICATION CD8+ T cells Molecular subtype MIBC 03 medical and health sciences DATA ANALYSIS SOFTWARE ADULT GENE MUTATION Genetics medicine CANCER PATIENT Biomarkers Tumor Humans KEGG IMMUNOTHERAPY ARTICLE EP300 030304 developmental biology ONCOLOGICAL PARAMETERS Bladder cancer TUMOR MUTATION BURDEN TMB TRANSFORMING GROWTH FACTOR BETA Research RYANODINE RECEPTOR 2 MUSCLE INVASIVE BLADDER CANCER medicine.disease ATEZOLIZUMAB lcsh:Genetics MOLECULAR SUBTYPE FIBROBLAST GROWTH FACTOR RECEPTOR 3 OVERALL SURVIVAL Urinary Bladder Neoplasms PROTEIN KINASE B Cancer research biology.protein E1A ASSOCIATED P300 PROTEIN TUMOR MARKER CD8 CLINICAL TRIAL (TOPIC) |
| Zdroj: | Hereditas Hereditas, Vol 158, Iss 1, Pp 1-12 (2021) |
| DOI: | 10.21203/rs.3.rs-54624/v2 |
| Popis: | Immunotherapy, especially anti-PD-1, is becoming a pillar of modern muscle-invasive bladder cancer (MIBC) treatment. However, the objective response rates (ORR) are relatively low due to the lack of precise biomarkers to select patients. Herein, the molecular subtype, tumor mutation burden (TMB), and CD8+ T cells were calculated by the gene expression and mutation profiles of MIBC patients. MIBC immunotypes were constructed using clustering analysis based on tumor mutation burden, CD8+ T cells, and molecular subtypes. Mutated genes, enriched functional KEGG pathways and GO terms, and co-expressed network-specific hub genes have been identified. We demonstrated that ORR of immunotype A patients identified by molecular subtype, CD8+ T cells, and TMB is about 36% predictable. PIK3CA , RB1 , FGFR3 , KMT2C , MACF1 , RYR2 , and EP300 are differentially mutated among three immunotypes. Pathways such as ECM-receptor interaction, PI3K-Akt signaling pathway, and TGF-beta signaling pathway are top-ranked in enrichment analysis. Low expression of ACTA2 was associated with the MIBC survival benefit. The current study constructs a model that could identify suitable MIBC patients for immunotherapy, and it is an important step forward to the personalized treatment of bladder cancers.Immunotherapy, especially anti-PD-1, is becoming a pillar of modern muscle-invasive bladder cancer (MIBC) treatment. However, the objective response rates (ORR) are relatively low due to the lack of precise biomarkers to select patients. Herein, the molecular subtype, tumor mutation burden (TMB), and CD8+ T cells were calculated by the gene expression and mutation profiles of MIBC patients. MIBC immunotypes were constructed using clustering analysis based on tumor mutation burden, CD8+ T cells, and molecular subtypes. Mutated genes, enriched functional KEGG pathways and GO terms, and co-expressed network-specific hub genes have been identified. We demonstrated that ORR of immunotype A patients identified by molecular subtype, CD8+ T cells, and TMB is about 36% predictable. PIK3CA , RB1 , FGFR3 , KMT2C , MACF1 , RYR2 , and EP300 are differentially mutated among three immunotypes. Pathways such as ECM-receptor interaction, PI3K-Akt signaling pathway, and TGF-beta signaling pathway are top-ranked in enrichment analysis. Low expression of ACTA2 was associated with the MIBC survival benefit. The current study constructs a model that could identify suitable MIBC patients for immunotherapy, and it is an important step forward to the personalized treatment of bladder cancers. |
| Databáze: | OpenAIRE |
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