中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 40 Issue 9
Sep.  2024
Turn off MathJax
Article Contents

Construction of a novel disulfidptosis-related prognostic model for patients with hepatocellular carcinoma based on bioinformatics analysis

DOI: 10.12449/JCH240917
Research funding:

The State Key Projects Specialized on Infectious Disease, Chinese Ministry of Science and Technology (2018ZX10725506);

Research and Translational Application of Clinical Characteristic Diagnosis and Treatment Technology in the Capital (Z221100007422002)

More Information
  • Corresponding author: YANG Yongping, yongpingyang@hotmail.com (ORCID: 0000-0002-8307-1095)
  • Received Date: 2023-12-25
  • Accepted Date: 2024-03-18
  • Published Date: 2024-09-25
  •   Objective  To investigate the expression of disulfidptosis-related genes in hepatocellular carcinoma (HCC) and the prognostic value of disulfidptosis in HCC, to construct a prognostic model, and to analyze its impact on the biological processes of HCC and sorafenib resistance.  Methods  The TCGA-LIHC database was used to collect the mRNA expression profiles and corresponding clinical data of HCC patients, and the LASSO-Cox regression algorithm was used to construct a four-gene predictive model for prognosis in the TCGA cohort. The external datasets ICGC and GSE14520 were used to validate the prognostic efficacy of the model, and the Cancer Drug Sensitivity Genomics (GDSC) data were used to investigate the value of the disulfidptosis model in predicting sorafenib treatment response, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to investigate the biological functions of disulfidptosis-related genes. The independent-samples t test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier curve and the log-rank test were used to evaluate the difference in prognosis, and univariate and multivariate Cox regression analyses were used to investigate whether risk score was an independent influencing factor for patient prognosis.  Results  The univariate Cox regression analysis in the TCGA cohort showed that seven known disulfidptosis-related genes were significantly associated with overall survival (OS) in HCC (all P<0.05). The LASSO-Cox regression analysis was used to construct a prognostic model based on disulfidptosis-related genes (DRG), and the risk score RS-DRG was calculated as RS-DRG=(0.061 6)×GYS1 expression level+(0.152 8)×LRPPRC expression level+(0.268 3)×RPN1 expression level+(0.183 5)×SLC7A11 expression level. The log-rank test showed that the patients with a high risk score based on the disulfidptosis model had a significantly lower OS than those with a low risk score (P<0.001). Based on the results of the multivariate Cox regression analysis, risk score was an independent predictive factor for OS in both TCGA and ICGC cohorts (TCGA: hazard ratio [HR]=1.869, P=0.002; ICGC: HR=3.469, P=0.004). The Spearman correlation analysis showed that RS-DRG was significantly positively correlated with the infiltration level of various immune cells (including B lymphocytes, CD4+ T lymphocytes, neutrophils, macrophages, and dendritic cells) in tumor microenvironment (all P<0.05). The patients in the high-risk score group had a significantly lower IC50 value of sorafenib and were more sensitive to sorafenib (P<0.001). The KEGG/GO enrichment analysis showed that the differentially expressed disulfidptosis-related genes were significantly enriched in various mitosis-related molecular functions.  Conclusion  This study constructed a novel prognostic model based on disulfidptosis-related genes, which has a potential clinical value in predicting the prognosis of HCC, and targeting disulfidptosis-related genes may provide a promising approach for HCC treatment.

     

  • loading
  • [1]
    CAO PB, YANG AQ, LI PY, et al. Genomic gain of RRS1 promotes hepatocellular carcinoma through reducing the RPL11-MDM2-p53 signaling[J]. Sci Adv, 2021, 7( 35): eabf4304. DOI: 10.1126/sciadv.abf4304.
    [2]
    FENG M, SURESH K, SCHIPPER MJ, et al. Individualized adaptive stereotactic body radiotherapy for liver tumors in patients at high risk for liver damage: A phase 2 clinical trial[J]. JAMA Oncol, 2018, 4( 1): 40- 47. DOI: 10.1001/jamaoncol.2017.2303.
    [3]
    WEI L, LEE D, LAW CT, et al. Genome-wide CRISPR/Cas9 library screening identified PHGDH as a critical driver for Sorafenib resistance in HCC[J]. Nat Commun, 2019, 10( 1): 4681. DOI: 10.1038/s41467-019-12606-7.
    [4]
    FENG MX, MA MZ, FU Y, et al. Elevated autocrine EDIL3 protects hepatocellular carcinoma from anoikis through RGD-mediated integrin activation[J]. Mol Cancer, 2014, 13: 226. DOI: 10.1186/1476-4598-13-226.
    [5]
    LIU XG, NIE LT, ZHANG YL, et al. Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis[J]. Nat Cell Biol, 2023, 25( 3): 404- 414. DOI: 10.1038/s41556-023-01091-2.
    [6]
    ZHENG PJ, ZHOU CT, DING YM, et al. Disulfidptosis: A new target for metabolic cancer therapy[J]. J Exp Clin Cancer Res, 2023, 42( 1): 103. DOI: 10.1186/s13046-023-02675-4.
    [7]
    ZHAO SY, WANG LY, DING W, et al. Crosstalk of disulfidptosis-related subtypes, establishment of a prognostic signature and immune infiltration characteristics in bladder cancer based on a machine learning survival framework[J]. Front Endocrinol(Lausanne), 2023, 14: 1180404. DOI: 10.3389/fendo.2023.1180404.
    [8]
    KUDO Y, SUGIMOTO M, ARIAS E, et al. PKCλ/ι loss induces autophagy, oxidative phosphorylation, and NRF2 to promote liver cancer progression[J]. Cancer Cell, 2020, 38( 2): 247- 262.e11. DOI: 10.1016/j.ccell.2020.05.018.
    [9]
    WU QC, ZHOU WH, YIN SY, et al. Blocking triggering receptor expressed on myeloid cells-1-positive tumor-associated macrophages induced by hypoxia reverses immunosuppression and anti-programmed cell death ligand 1 resistance in liver cancer[J]. Hepatology, 2019, 70( 1): 198- 214. DOI: 10.1002/hep.30593.
    [10]
    CALDERARO J, ZIOL M, PARADIS V, et al. Molecular and histological correlations in liver cancer[J]. J Hepatol, 2019, 71( 3): 616- 630. DOI: 10.1016/j.jhep.2019.06.001.
    [11]
    ZHONG ZY, ZHANG CJ, NI S, et al. NFATc1-mediated expression of SLC7A11 drives sensitivity to TXNRD1 inhibitors in osteoclast precursors[J]. Redox Biol, 2023, 63: 102711. DOI: 10.1016/j.redox.2023.102711.
    [12]
    FAVARO E, BENSAAD K, CHONG MG, et al. Glucose utilization via glycogen phosphorylase sustains proliferation and prevents premature senescence in cancer cells[J]. Cell Metab, 2012, 16( 6): 751- 764. DOI: 10.1016/j.cmet.2012.10.017.
    [13]
    XIE H, SONG J, GODFREY J, et al. Glycogen metabolism is dispensable for tumour progression in clear cell renal cell carcinoma[J]. Nat Metab, 2021, 3( 3): 327- 336. DOI: 10.1038/s42255-021-00367-x.
    [14]
    LIU JY, CHEN YJ, FENG HH, et al. LncRNA SNHG17 interacts with LRPPRC to stabilize c-Myc protein and promote G1/S transition and cell proliferation[J]. Cell Death Dis, 2021, 12( 11): 970. DOI: 10.1038/s41419-021-04238-x.
    [15]
    WANG HH, TANG AM, CUI YY, et al. LRPPRC facilitates tumor progression and immune evasion through upregulation of m6A modification of PD-L1 mRNA in hepatocellular carcinoma[J]. Front Immunol, 2023, 14: 1144774. DOI: 10.3389/fimmu.2023.1144774.
    [16]
    LIU XY, XIAO WD, ZHANG YN, et al. Reversible phosphorylation of Rpn1 regulates 26S proteasome assembly and function[J]. Proc Natl Acad Sci USA, 2020, 117( 1): 328- 336. DOI: 10.1073/pnas.1912531117.
    [17]
    CHEN X, KANG R, KROEMER G, et al. Broadening horizons: The role of ferroptosis in cancer[J]. Nat Rev Clin Oncol, 2021, 18( 5): 280- 296. DOI: 10.1038/s41571-020-00462-0.
  • 附录A 和B 见二维码.pdf
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(9)

    Article Metrics

    Article views (67) PDF downloads(10) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return