Single-cell intratumoral stemness analysis reveals the involvement of cell cycle and DNA damage repair in two different types of esophageal cancer

Abstract

Intratumoral heterogeneity, particularly the potential cancer stemness of single cancer cells, has not yet been fully elucidated in human esophageal cancer. Single-cell transcriptome sequencing of two types of esophageal adenocarcinoma (EAC) and two types of esophageal squamous cell carcinoma (ESCC) tissues was performed, and the intratumoral cancer stemness of the types of esophageal cancer were characterized at the single-cell level in the present study. By comparing the transcriptomic profiles of single cancer cells with high and low stemness in individual patients, it was revealed that the overexpression of cell cycle-associated genes in EAC cells was highly correlated with stemness, whereas overexpression of genes involved in the signaling pathways of DNA replication and DNA damage repair was significantly correlated with stemness in ESCC. High expression of these stemness-associated genes was correlated with poor prognosis of patients. Additionally, poly [ADP-ribose] polymerase(PARP)4 was identified as a novel cancer stemness-associated gene in ESCC and its association with survival was validated in a cohort of 121 patients with ESCC. These findings have profound potential implications for the use of cell cycle inhibitors in EAC and PARP inhibitors in ESCC, which may provide novel mechanistic insights into the plasticity of esophageal cancer.