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Tumor Discovery DRGs in HCC prognosis and immunity

outcomes of treatment remain suboptimal, with only 15% approach to disease treatment. For example, intracellular
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of patients surviving for 5 years. In China, liver cancer disulfidptosis has been associated with oxidative stress,
2
is the third most common cancer and the second leading and the formation of invasive pseudopods in metastatic
cause of cancer-related mortality. Most patients succumb tumors has been suggested to exacerbate disulfide bonding
3
to tumor progression and recurrence despite receiving stress. Disulfide production is regulated by several
16
aggressive treatment modalities such as chemotherapy signaling pathways, including the nuclear factor kappa B
and surgical resection. Nevertheless, research suggests and c-Jun N-terminal kinase pathways. In cardiovascular
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4,5
that immune checkpoint inhibitor (ICI) therapy offers diseases, cellular damage has been mitigated by inhibiting
novel therapeutic options for HCC by targeting various sulfur dioxide. Thus, disulfidptosis is considered to hold
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cancers. However, studies have not identified any significant potential as a therapeutic strategy. However, the
6,7
prognostic biomarkers for ICI therapy. Consequently, role of disulfidptosis in HCC remains unclear. Hence, in
identifying reliable biomarkers for ICIs in HCC remains this study, DRGs were identified to develop a risk score
of utmost importance. model. Genes associated with DRGs were screened using
univariate Cox regression and least absolute shrinkage
Disulfidptosis, a recently described form of metabolism-
associated regulated cell death, was identified in February and selection operator (LASSO) regression analyses.
A risk model was developed, and its predictive ability was
2023 in a study by Liu et al. It is associated with disulfide assessed. The association between prognostic and clinical
8
linkages between internal and external protein molecules. features was examined, followed by functional enrichment
Disulfide stress, caused by the accumulation of disulfide- analysis and the construction of a protein-protein
bonded substances in cancer cells with elevated SLC7A11 interaction (PPI) network. Gene set enrichment analysis
expression and glucose deprivation, disrupts the normal (GSEA) and immune infiltration correlation analyses were
binding of disulfide bonds between cytoskeletal proteins. performed to investigate the expression levels of immune
This disruption induces conformational and functional checkpoint genes and DRGs in HCC and normal tissues. In
alterations in proteins, ultimately leading to cell death. addition, the gene expression and drug sensitivity profiles
8
Research has revealed that the SLC7A11 gene plays a of DRG-related genes in tumors were analyzed. These
significant role in disulfidptosis, primarily influencing signaling pathway genes have potential as therapeutic
the development of specific malignancies and anti-tumor targets due to their roles as oncogenes. To elucidate the
immunity. Disulfidptosis is anticipated as a potential role of disulfidptosis in HCC, our study aims to explore the
cancer treatment, given that previous research has association between DRGs and both the immunological
demonstrated the widespread expression of the SLC7A11 profiles and clinical prognosis of HCC patients.
gene in numerous cancer cells. Disulfidptosis-related genes
9
(DRGs) have been used to screen for prognostic markers 2. Data and methods
and potential therapeutic targets in various malignancies,
such as colorectal adenocarcinoma. In addition, DRGs 2.1. Materials and data
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have been associated with the development of HCC. 2.1.1. Data collection
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Furthermore, numerous studies have demonstrated that Clinical data for 424 patients with HCC were obtained
SLC7A11 is associated with cell death across various organs from the Cancer Genome Atlas (TCGA) database
and tissues in the human body. For example, tumor growth (https://portal.gdc.cancer.gov/). Data from the 424 TCGA-
has been promoted by the overexpression of SLC7A11, liver HCC samples were standardized using the “Surrogate
partly due to the suppression of ferroptosis, while Variable Analysis” package in R software (version R 4.4.2).
inhibition of SLC7A11 is more likely to induce autophagic Subsequently, 79 immune checkpoint-associated
death and apoptosis as a result of elevated intracellular genes were identified from the review, along with 23
19
reactive oxygen species levels. The downregulation of differentially regulated genes (SLC7A11, ACTN4, GYS1,
12
SLC7A11 has been shown to impair the cysteine metabolic MYH10, NDUFS1, IQGAP1, MYL6, NDUFA11, PDLIM1,
pathway, affecting glutathione synthesis, which leads to NUBPL, NCKAP1, CD2AP, LRPPRC, INF2, SLC3A2,
the accumulation of lipid peroxides and ultimately causes MYH9, RPN1, ACTB, CAPZB, DSTN, FLNA, FLNB, and
ferroptosis cell death. 13 TLN1) reported by Liu et al. The mRNA expression data
8
Elevated SLC7A11 expression has been found to activate were normalized using the appropriate R package. A total
the phosphatidylinositol 3-kinase/protein kinase B (PI3K/ of 23 genes were selected based on the criteria of |logFC|
Akt) pathway, promoting the migration and invasion > 0.5 and false discovery rate (FDR)< 0.05. Differentially
of pancreatic cancer cells. Moreover, the mechanisms expressed genes were initially identified using the “limma”
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of disulfidptosis have been proposed as a critical new package in R software, identifying 18 DRGs (Figure 1).

Volume 4 Issue 2 (2025) 67 doi: 10.36922/td.8214