Research Paper Volume 13, Issue 4 pp 5928—5945

Cell differentiation trajectory predicts patient potential immunotherapy response and prognosis in gastric cancer

Renshen Xiang1,2, *, , Yuping Rong1, *, , Yuhang Ge1, , Wei Song1,2, , Jun Ren1,2, , Tao Fu1, ,

  • 1 Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
  • 2 The Central Laboratory of the First Clinical College of Wuhan University, Wuhan 430060, Hubei Province, China
* Equal contribution

Received: November 16, 2020       Accepted: December 29, 2020       Published: February 17, 2021
How to Cite

Copyright: © 2021 Xiang 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.


The purpose of this study was to investigate the differentiation trajectory of gastric cancer (GC) cells and its clinical relevance and generate a prognostic risk scoring (RS) signature based on GC differentiation-related genes (GDRGs) to predict overall survival (OS). Integrated single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from GC samples were used for analysis. The cell differentiation trajectory analysis identified three subsets with distinct differentiation states, of which subsets I/II were involved in metabolic disorders, subset II were also associated with hypoxia tolerance, and subset III were related to immune-related pathways. GC samples were divided into three GDRG-based molecular subtypes, and it was found that molecular typing based on cell differentiation successfully predicted patient OS, clinicopathological features, immune infiltration status, and immune checkpoint gene expression. An eight-GDRG-based prognostic RS signature was generated, and the OS of the high-risk group was significantly worse than that of the low-risk group. By integrating the GDRG-based RS signature with prognostic clinicopathological characteristics, a clinicopathologic-genomic nomogram was constructed, and this nomogram yielded strong predictive performance and high accuracy. The study highlights the implication of GC cell differentiation for predicting patient clinical outcome and potential immunotherapy response and proposes a promising treatment direction for GC.


GC: Gastric cancer; GDRG: GC differentiation-related gene; TCGA: The Cancer Genome Atlas; RS: Risk scoring; OS: Overall survival; ScRNA-seq: Single-cell RNA sequencing; GEO: Gene Expression Omnibus; PCA: Principal component analysis; PC: Principal component; WGCNA: Weighted correlation network analysis; FDR: False discovery rate; GO: Gene Ontology; BP: Biological process; KEGG: Kyoto Encyclopedia of Genes and Genomes; CDF: Cumulative distribution function; ICG: Immune checkpoint gene; ROC: Receiver operating characteristic; ACRG: Asian Cancer Research Group.