Title:Integrating Single-cell and Bulk RNA Sequencing Reveals Stemness
Phenotype Associated with Clinical Outcomes and Potential Immune
Evasion Mechanisms in Hepatocellular Carcinoma
Volume: 19
Issue: 4
Author(s): Xiaojing Zhu, Jiaxing Zhang, Zixin Zhang, Hongyan Yuan, Aimin Xie, Nan Zhang, Minwei Wang, Minghui Jiang, Yanqi Xiao, Hao Wang, Xing Wang and Yan Xu*
Affiliation:
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
Keywords:
Stemness, immune evasion, prognosis, cell interactions, recurrence, hepatocellular carcinoma, single-cell.
Abstract:
Aims: Bulk and single-cell RNA sequencing data were analyzed to explore the association
of stemness phenotype with dysfunctional anti-tumor immunity and its impact on clinical outcomes
of primary and relapse HCC.
Background: The stemness phenotype is gradually acquired during cancer progression; however, it
remains unclear the effect of stemness phenotype on recurrence and clinical outcomes in hepatocellular
carcinoma (HCC).
Methods: The stemness index (mRNAsi) calculated by a one-class logistic regression algorithm in
multiple HCC cohorts was defined as the stemness phenotype of the patient. Using single-cell profiling
in primary or early-relapse HCC, cell stemness phenotypes were evaluated by developmental potential.
Differential analysis of stemness phenotype, gene expression and interactions between primary
and recurrent samples revealed the underlying immune evasion mechanisms.
Results: A strong correlation was discovered between mRNAsi and clinical outcomes in patient with
HCC. The high and low mRNAsi groups had distinct tumor immune microenvironments. Cellular
stemness phenotype varied by cell type. Moreover, compared with primary tumors, early-relapse tumors
had increased stemness of dendritic cells and tumor cells and reduced stemness of T cells and B
cells. Moreover, in relapse tumors, CD8+ T cells displayed a low stemness state, with a high exhausted
state, unlike the high stemness state observed in primary HCC.
Conclusions: The comprehensive characterization of the HCC stemness phenotype provides insights
into the clinical outcomes and immune escape mechanisms associated with recurrence.
