Single-cell RNA sequencing reveals the epithelial cell heterogeneity and invasive subpopulation in human bladder cancer

Int J Cancer. 2021 Dec 15;149(12):2099-2115. doi: 10.1002/ijc.33794. Epub 2021 Sep 16.

Abstract

Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell invasion and crosstalks within bladder tumor cells has not been determined. Here, we applied droplet-based single-cell RNA sequencing (scRNA-seq) to acquire transcriptional profiles of 36 619 single cells isolated from seven patients. Single cell transcriptional profiles matched well with the pathological basal/luminal subtypes. Notably, in T1 tumors diagnosed as luminal subtype, basal cells displayed characteristics of epithelial-mesenchymal transition (EMT) and mainly located at the tumor-stromal interface as well as micrometastases in the lamina propria. In one T3 tumor, muscle-invasive tumor showed significantly higher expression of cancer stem cell markers SOX9 and SOX2 than the primary tumor. We additionally analyzed communications between tumor cells and demonstrated its relevance to basal/luminal phenotypes. Overall, our single-cell study provides a deeper insight into the tumor cell heterogeneity associated with bladder cancer progression.

Keywords: bladder cancer; intratumoral heterogeneity; single-cell RNA sequencing; tumor cells communication; tumor invasion.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Disease Progression
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Muscle, Smooth / pathology
  • Neoplasm Invasiveness / genetics
  • RNA-Seq
  • Single-Cell Analysis
  • Tomography, X-Ray Computed
  • Urinary Bladder / cytology
  • Urinary Bladder / diagnostic imaging
  • Urinary Bladder / pathology*
  • Urinary Bladder Neoplasms / diagnosis
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology

Substances

  • Biomarkers, Tumor