Landscape of the intratumroal microenvironment in bladder cancer: Implications for prognosis and immunotherapy

Elsevier

Available online 1 December 2022

Computational and Structural Biotechnology JournalAuthor 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.

AbstractIntroduction

This 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.

Methods

The 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.

Results

The 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.

Conclusions

The newly established BCIPI is a valuable tool for predicting overall survival outcomes and immunotherapeutic responses in patients with bladder cancer.

AbbreviationsBCG

Bacillus Calmette-Guerin

FDA

Food and Drug Administration

CNVs

Copy number variations

MES

Mesenchymal transition

AJCC

American Joint Committee on Cancer

ICI

Immune checkpoint inhibitor

Anti-PD-L1

Antitumor response to atezolizumab

FPKM

Fragments per kilobase per million

TPM

Transcripts per kilobase million

RMA

Robust multiarray average

NES

Normalized enrichment score

BCIPI

Bladder cancer immune prognostic index

RMS

Restricted mean survival

Keywords

Bladder 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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