Development and validation of an intra-tumor heterogeneity-related signature to predict prognosis of bladder cancer: a study based on single-cell RNA-seq

作者：Ranran Zhou, Jingjing Liang, Qi Chen, Hu Tian, Cheng Yang, Cundong Liu · 发表于：Aging · 年份：2021 · DOI：10.18632/aging.203353 · 被引用次数：19 · 研究领域：Bladder and Urothelial Cancer Treatments、Ferroptosis and cancer prognosis、Epigenetics and DNA Methylation

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.