Research Paper Volume 13, Issue 15 pp 19415—19441
Development and validation of an intra-tumor heterogeneity-related signature to predict prognosis of bladder cancer: a study based on single-cell RNA-seq
- 1 Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
- 2 The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China
- 3 Department of Cardiology, Shunde Hospital of Southern Medical University, Foshan, China
Received: May 9, 2021 Accepted: July 15, 2021 Published: August 2, 2021
https://doi.org/10.18632/aging.203353How to Cite
Copyright: © 2021 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Intra-tumor heterogeneity (ITH) was a potential mechanism of progression and drug resistance in bladder cancer (BCa). However, the understanding of ITH in BCa remains insufficient. Single-cell RNA sequencing (scRNA-seq) profiles of 2075 cells were analyzed, and 2940 cell markers were screened. The ITH of 396 cases was evaluated, and 96 ITH-related genes were identified. Based on the gene-pair strategy, 96 genes were cyclically paired, and an 8-gene-pair model was successfully established to evaluate the overall survival of BCa through Lasso and multivariate Cox regressions. The risk model showed high predictive value in the training dataset (n = 396, p = 0) and external validation datasets (n = 165, p = 2.497e-02; n = 224, p = 3.423e-02). The model was also valuable for the prediction of clinical treatment outcomes. Totally, a prognostic model based on scRNA-seq and ITH was successfully constructed and validated in large cohorts, providing novel clues for ITH study of BCa.