Abstract
Background
Cancer stem cells (CSCs) were linked to cancer aggressiveness and poor prognosis in patients with hepatocellular carcinoma (HCC).
Methods
We integrated two external HCC cohorts to develop the stem cell subtypes according to unsupervised clustering with 26 stem cell gene sets. Between the subtypes, differences in prognosis, clinical characteristics, recognized HCC subtypes, metabolic profile, immune-related features, somatic mutation, and drug sensitivity were examined. The prognostic signature was created, and validated by numerous cohorts, and used to assess the efficacy of immunotherapy and transcatheter arterial chemoembolization (TACE) treatment. The nomogram was developed based on the signature and clinical features. We further examined the function of KIF20A in HCC and proved that KIF20A had the potential to regulate the stemness of HCC cells through western blot.
Results
Low stem cell patterns, a good prognosis, positive clinical features, specific molecular subtypes, low metastatic characteristics, and an abundance of metabolic and immunological aspects were associated with Cluster 1, whereas Cluster 2 was the reverse. Chemotherapy and immunotherapy were more effective in Cluster 1. Cluster 1 and CTNNB1 and ALB mutation were more closely. Additionally, the prognosis, immunotherapeutic, and TACE therapy responses were all worse in the high-risk group. The nomogram could predict the survival probability of HCC patients. KIF20A was discovered to be overexpressed in HCC and was revealed to be connected to the stemness of the HepG2 cell line.
Conclusions
Two stem cell subgroups with different prognoses, metabolic, and immunological characteristics in HCC patients were identified. We also created a 7-gene prognostic signature and a nomogram to estimate the survival probability. The function of KIF20A in HCC stemness was initially examined.
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Availability of data and materials
The data are available from the corresponding author for reasonable requests.
Abbreviations
- AUCs:
-
Area under curves
- BP:
-
Biological processes
- CSCs:
-
Cancer stem cells
- CAFs:
-
Cancer-associated fibroblasts
- CNV:
-
Copy number variation
- DE:
-
Differentially expressed
- DSS:
-
Disease-special survival
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- FBS:
-
Fetal bovine serum
- HCC:
-
Hepatocellular carcinoma
- HRD:
-
Homologous recombination deficiency
- hCAR:
-
Human constitutive androstane receptor
- ICB:
-
Immune checkpoint blockade
- ITH:
-
Intra-tumor heterogeneity
- KM:
-
Kaplan–Meier
- KEGG:
-
Kyoto encyclopedia of genes and genomes
- LOH:
-
Loss of heterozygosity
- NTP:
-
Nearest template prediction
- NC:
-
Negative control
- OS:
-
Overall survival
- PCA:
-
Principal component analysis
- PFS:
-
Progression-free survival
- RT-PCR:
-
Real-time polymerase chain reaction
- RFS:
-
Recurrence-free survival
- siRNA:
-
Small interfering RNA
- tSNE:
-
T-distributed stochastic neighbor embedding
- TACE:
-
Transcatheter arterial chemoembolization
- TME:
-
Tumor microenvironment
- TMB:
-
Tumor mutation burden
- WB:
-
Western blot
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CQ: supervision, project administration, data curation, and writing—original draft. WS: formal analysis, data curation, investigation, writing—original draft. HW: investigation, and writing—original draft.
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Qiu, C., Wu, H. & Shi, W. Characterization of stem cell subtypes and prognostic signature in hepatocellular carcinoma. J Cancer Res Clin Oncol 149, 14081–14100 (2023). https://doi.org/10.1007/s00432-023-05239-3
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DOI: https://doi.org/10.1007/s00432-023-05239-3