Available online 1 December 2022
Author links open overlay panelHighlights:•Our study presents the landscape of intratumoral microenvironment in bladder cancer (BCa);
•The BCa immune prognostic index (BCIPI) is a promising biomarker in estimating overall survival for BCa patients;
•Patients with high BCIPI exhibited potential therapeutic benefits from anti-PD-L1 immunotherapy;
•BCIPI-High and -Low subgroups showed significant differences in the pathway, tumor infiltrated immunocyte, gene mutation, copy number variation levels, etc., offering inspiration for mechanism investigations.
AbstractIntroductionThis study aims to present the landscape of the intratumoral microenvironment and by which establish a classification system that can be used to predict the prognosis of bladder cancer patients and their response to anti-PD-L1 immunotherapy.
MethodsThe expression profiles of 888 bladder cancer cases were downloaded from four public datasets. Single-sample gene set enrichment analysis (ssGSEA), univariate Cox regression analysis, and meta-analysis were employed to establish the bladder cancer immune prognostic index (BCIPI). Extensive analyses were executed to investigate the association between BCIPI and overall survival, tumor-infiltrated immunocytes, immunotherapeutic response, mutation load, etc.
ResultsThe results obtained from four independent cohorts and meta-analyses suggested that the BCIPI is an effective classification system for estimating bladder cancer patients’ overall survival. Patients in the BCIPI-High subgroup revealed different immunophenotypic outcomes from those in the BCIPI-Low subgroup regarding tumor-infiltrated immunocytes and mutated genes. Subsequent analysis suggested that patients in the BCIPI-High subgroup were more sensitive to anti-PD-L1 immunotherapy than those in the BCIPI-Low subgroup.
ConclusionsThe newly established BCIPI is a valuable tool for predicting overall survival outcomes and immunotherapeutic responses in patients with bladder cancer.
AbbreviationsBCGBacillus Calmette-Guerin
FDAFood and Drug Administration
CNVsCopy number variations
MESMesenchymal transition
AJCCAmerican Joint Committee on Cancer
ICIImmune checkpoint inhibitor
Anti-PD-L1Antitumor response to atezolizumab
FPKMFragments per kilobase per million
TPMTranscripts per kilobase million
RMARobust multiarray average
NESNormalized enrichment score
BCIPIBladder cancer immune prognostic index
RMSRestricted mean survival
KeywordsBladder cancer
genomic
immunotherapy
overall survival
© 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
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