Please use this identifier to cite or link to this item: http://hdl.handle.net/10995/103195
Title: Defining muscle-invasive bladder cancer immunotypes by introducing tumor mutation burden, CD8+ T cells, and molecular subtypes
Authors: Chen, Z.
Liu, G.
Liu, G.
Bolkov, M. A.
Shinwari, K.
Tuzankina, I. A.
Chereshnev, V. A.
Wang, Z.
Issue Date: 2021
Publisher: BioMed Central Ltd
Citation: Defining muscle-invasive bladder cancer immunotypes by introducing tumor mutation burden, CD8+ T cells, and molecular subtypes / Z. Chen, G. Liu, G. Liu, et al. — DOI 10.1186/s41065-020-00165-7 // Hereditas. — 2021. — Vol. 158. — Iss. 1. — 1.
Abstract: 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. © 2021, The Author(s).
Keywords: CD8+ T CELLS
IMMUNOTHERAPY
IMMUNOTYPE
MIBC
MOLECULAR SUBTYPE
TMB
ATEZOLIZUMAB
E1A ASSOCIATED P300 PROTEIN
FIBROBLAST GROWTH FACTOR RECEPTOR 3
PHOSPHATIDYLINOSITOL 3 KINASE
PROTEIN KINASE B
RYANODINE RECEPTOR 2
TRANSFORMING GROWTH FACTOR BETA
TUMOR MARKER
ADULT
ARTICLE
CANCER CLASSIFICATION
CANCER IMMUNOTHERAPY
CANCER PATIENT
CANCER SURVIVAL
CD8+ T LYMPHOCYTE
CELL INFILTRATION
CLINICAL TRIAL (TOPIC)
DATA ANALYSIS SOFTWARE
GENE EXPRESSION
GENE MUTATION
GENE ONTOLOGY
HUMAN
HUMAN CELL
MOLECULAR SUBTYPE
MUSCLE INVASIVE BLADDER CANCER
ONCOLOGICAL PARAMETERS
OVERALL SURVIVAL
PI3K/AKT SIGNALING
TGF BETA SIGNALING
TUMOR MUTATION BURDEN
URI: http://hdl.handle.net/10995/103195
Access: info:eu-repo/semantics/openAccess
SCOPUS ID: 85098627194
PURE ID: 20382726
355d1a0b-a6ea-4399-80e2-41498fb9679e
ISSN: 180661
DOI: 10.1186/s41065-020-00165-7
metadata.dc.description.sponsorship: This study was funded by the Act 211 Government of the Russian Federation (No.02.A03.21.0006) and the IIP UB RAS project (No.AAAA-A18–118020590108-7).
Appears in Collections:Научные публикации, проиндексированные в SCOPUS и WoS CC

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