PMID- 36937389
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230321
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 13
DP  - 2023
TI  - Hepatocellular carcinoma subtypes based on metabolic pathways reveals potential 
      therapeutic targets.
PG  - 1086604
LID - 10.3389/fonc.2023.1086604 [doi]
LID - 1086604
AB  - INTRODUCTION: Hepatocellular carcinoma (HCC) is an aggressive malignancy with 
      steadily increasing incidence rates worldwide and poor therapeutic outcomes. 
      Studies show that metabolic reprogramming plays a key role in tumor genesis and 
      progression. In this study, we analyzed the metabolic heterogeneity of epithelial 
      cells in the HCC and screened for potential biomarkers. METHODS: The hepatic 
      single-cell RNA sequencing (scRNA-seq) datasets of HCC patients and healthy 
      controls were obtained from the Gene Expression Omnibus (GEO) database. Based on 
      data intergration and measurement of differences among groups, the metabolic 
      epithelial cell subpopulations were identified. The single-cell metabolic pathway 
      was analyzed and the myeloid subpopulations were identified. Cell-cell 
      interaction analysis and single-cell proliferation analysis were performed. The 
      gene expression profiles of HCC patients were obtained from the GSE14520 dataset 
      of GEO and TCGA-LIHC cohort of the UCSC Xena website. Immune analysis was 
      performed. The differentially expressed genes (DEGs) were identified and 
      functionally annotated. Tumor tissues from HCC patients were probed with 
      anti-ALDOA, anti-CD68, anti-CD163, anti-CD4 and anti-FOXP3 antibodies. Results We 
      analyzed the scRNA-seq data from 48 HCC patients and 14 healthy controls. The 
      epithelial cells were significantly enriched in HCC patients compared to the 
      controls (p = 0.011). The epithelial cells from HCC patients were classified into 
      two metabolism-related subpopulations (MRSs) - pertaining to amino acid 
      metabolism (MRS1) and glycolysis (MRS2). Depending on the abundance of these 
      metabolic subpopulations, the HCC patients were also classified into the MRS1 and 
      MRS2 subtype distinct prognoses and immune infiltration. The MRS2 group had 
      significantly worse clinical outcomes and more inflamed tumor microenvironment 
      (TME), as well as a stronger crosstalk between MRS2 cells and immune 
      subpopulations that resulted in an immunosuppressive TME. We also detected high 
      expression levels of ALDOA in the MRS2 cells and HCC tissues. In the clinical 
      cohort, HCC patients with higher ALDOA expression showed greater enrichment of 
      immunosuppressive cells including M2 macrophages and T regulatory cells. 
      DISCUSSION: The glycolytic subtype of HCC cells with high ALDOA expression is 
      associated with an immunosuppressive TME and predicts worse clinical outcomes, 
      providing new insights into the metabolism and prognosis of HCC.
CI  - Copyright (c) 2023 He, Chen, He, Cao, Yao, Huang and Zheng.
FAU - He, Zehua
AU  - He Z
AD  - College of Life Science and Technology, Guangxi University, Nanning, Guangxi, 
      China.
FAU - Chen, Qingfeng
AU  - Chen Q
AD  - School of Computer, Electronic and Information, Guangxi University, Nanning, 
      Guangxi, China.
FAU - He, Wanrong
AU  - He W
AD  - Department of Gastroenterology, People's Hospital of Guangxi, Zhuang Autonomous 
      Region, Nanning, Guangxi, China.
FAU - Cao, Junyue
AU  - Cao J
AD  - College of Life Science and Technology, Guangxi University, Nanning, Guangxi, 
      China.
FAU - Yao, Shunhan
AU  - Yao S
AD  - Medical College, Guangxi University, Nanning, Guangxi, China.
FAU - Huang, Qingqiang
AU  - Huang Q
AD  - Guigang City Department of Radiology, People's Hospital, Guigang, Guangxi, China.
FAU - Zheng, Yu
AU  - Zheng Y
AD  - Department of Computer Science and Information Technology, La Trobe University, 
      Melbourne, VIC, Australia.
LA  - eng
PT  - Journal Article
DEP - 20230302
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC10017446
OTO - NOTNLM
OT  - bioinformatics
OT  - hepatocellular carcinoma (HCC)
OT  - metabologenomics
OT  - microenvironment
OT  - targeted therapy
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/03/21 06:00
MHDA- 2023/03/21 06:01
PMCR- 2023/01/01
CRDT- 2023/03/20 04:04
PHST- 2022/11/01 00:00 [received]
PHST- 2023/02/10 00:00 [accepted]
PHST- 2023/03/20 04:04 [entrez]
PHST- 2023/03/21 06:00 [pubmed]
PHST- 2023/03/21 06:01 [medline]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2023.1086604 [doi]
PST - epublish
SO  - Front Oncol. 2023 Mar 2;13:1086604. doi: 10.3389/fonc.2023.1086604. eCollection 
      2023.