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Constructing a disulfidptosis-related prognostic signature of hepatocellular carcinoma based on single-cell sequencing and weighted co-expression network analysis

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Abstract

Hepatocellular carcinoma (HCC) ranks as the second leading cause of cancer-related deaths globally. Disulfidptosis is a newly identified form of regulated cell death that is induced by glucose starvation. However, the clinical prognostic characteristics of disulfidptosis-associated genes in HCC remain poorly understood. We conducted an analysis of the single-cell datasets GSE149614 and performed weighted co-expression network analysis (WGCNA) on the Cancer Genome Atlas (TCGA) datasets to identify the genes related to disulfidptosis. A prognostic model was constructed using univariate COX and Lasso regression. Survival analysis, immune microenvironment analysis, and mutation analysis were performed. Additionally, a nomogram associated with disulfidptosis-related signature was constructed to identify the prognosis of HCC patients. Patients with HCC in the TCGA and GSE14520 datasets were categorized using a disulfidptosis-related model, revealing significant differences in survival times between the high- and low-disulfidptosis groups. High-disulfidptosis patients exhibited increased expression of immune checkpoint-related genes, implying that immunotherapy and certain chemotherapies may be beneficial for them. Meanwhile, the ROC and decision curves analysis (DCA) indicated that the nomogram has satisfying prognostic efficacy. Moreover, the experimental results of GATM in this prognostic model indicated that GATM is low expressed in HCC tissues, and GATM knockdown promotes the proliferation and migration of HCC cells. By analyzing single-cell and bulk multi-omics sequencing data, we developed a prognostic signature related to disulfidptosis and explored the relationship between high- and low-disulfidptosis groups in HCC. This study offers a novel reference for gaining a deeper understanding of the role of disulfidptosis in HCC.

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Data availability

This study analyzed publicly available datasets. The data were derived from TCGA-LIHC database, and the GSE149614 and GSE14520 in the GEO database, respectively.

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Acknowledgements

Thanks to TCGA and GEO databases and uploaders of the dataset.

Funding

This research was supported by the National Natural Science Foundation of China (No.82102512).

Author information

Author notes

  1. Zelin Tian and Junbo Song contributed equally to this work.

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China

    Zelin Tian & Junbo Song

  2. Department of Orthopedics, Ninth Hospital of Xi’an, Xi’an, 710000, Shaanxi, China

    Jiang She & Bingchen Dong

  3. Department of Urology, Air Force Medical University, Xi’an, China

    Weixiang He

  4. Department of Physiology and Pathophysiology, Air Force Medical University, Xi’an, China

    Shanshan Guo

Authors
  1. Zelin Tian
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  2. Junbo Song
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Contributions

Zelin Tian: Conceptualization (equal); Data curation (equal); Investigation (equal); Methodology (equal); Validation (equal); Visualization (equal); Writing-original draft (equal); Writing-review & editing (equal). Junbo Song: Conceptualization (equal); Data curation (equal); Investigation (equal); Methodology (equal); Validation (equal). Jiang She: Data curation (equal); Investigation (equal); Validation (equal); Visualization (equal). Weixiang He: Project administration (equal); Supervision (equal); Validation (equal). Shanshan Guo: Methodology (equal); Supervision (equal); Validation (equal); Resources (equal); Funding acquisition (equal); Writing-review & editing (equal). Bingchen Dong: Conceptualization (equal); Project administration (equal); Resources (equal); Supervision (equal); Writing-review & editing (equal).

Corresponding author

Correspondence to Bingchen Dong.

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Ethical approval

The studies involving humans were approved by the Ethics Committee in Xijing Hospital of Air Force Medical University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

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The authors declare no competing interests.

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Supplementary Information

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Supplementary file1 (DOCX 15 KB)

10495_2024_1968_MOESM2_ESM.tif

Supplementary file2. Figure S1 A heat map was generated to display the infiltration of immune cells in both the high disulfidptosis group and the low disulfidptosis group (TIF 15.2 MB)

10495_2024_1968_MOESM3_ESM.tif

Supplementary file3. HMGCS2, CFHR2, CFB, ALDH2, GATM, TTR and PCK1 were down-regulated in HCC tissues from the HPA database. (A)HMGCS2, Antibody HPA027442; (B)CFHR2, Antibody HPA038915; (C)CFB, Antibody HPA001817; (D)APOA1, Antibody HPA046715; (E)ALDH2, Antibody HPA051065; (F)GATM, Antibody HPA026077; (G)TTR, Antibody CAB002517; (H)PCK1, Antibody HPA006277 (TIF 26.3 MB)

Supplementary file4 (XLSX 11 KB)

Supplementary file5 (DOCX 15 KB)

Supplementary file6 (XLSX 10 KB)

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Tian, Z., Song, J., She, J. et al. Constructing a disulfidptosis-related prognostic signature of hepatocellular carcinoma based on single-cell sequencing and weighted co-expression network analysis. Apoptosis (2024). https://doi.org/10.1007/s10495-024-01968-z

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