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Characterization of stem cell subtypes and prognostic signature in hepatocellular carcinoma

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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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Acknowledgements

The authors would like to thank all the public databases included in this study.

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Author notes

  1. Chenjie Qiu and Huili Wu contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Changzhou Hospital of Traditional Chinese Medicine, Changzhou, China

    Chenjie Qiu

  2. Department of Endodontics, Changzhou Hospital of Traditional Chinese Medicine, Changzhou, China

    Huili Wu

  3. Department of Pediatric Cardiology, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Wenxiang Shi

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  1. Chenjie Qiu
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  2. Huili Wu
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  3. Wenxiang Shi
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Contributions

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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Correspondence to Chenjie Qiu or Wenxiang Shi.

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It was approved by Changzhou Hospital of Traditional Chinese Medicine’s Research Ethics Committee.

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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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