A novel disulfidptosis-related immune checkpoint genes signature: forecasting the prognosis of hepatocellular carcinoma

Abstract

Background HCC is an extremely malignant tumor with a very poor prognosis. In 2023, a brand-new kind of cell death known as disulfidptosis was identified. Although, the prognosis as well as expression of immune checkpoints that are closely connected with it in HCC remain unknown. Methods In this work, we identified 49 genes with abnormal expression in liver cancer and normal liver tissue, with 23 of them being differentially expressed genes. To create a signature, we classified all HCC cases into three subtypes and used the TCGA database to evaluate each relevant gene’s prognostic value for survival. Results Five gene signatures were identified using the LASSO Cox regression approach, while those diagnosed with HCC were split into either low- or high-risk groups. Patients having low-risk HCC showed a much greater likelihood of surviving than those with high risk (p < 0.05). Through immune cell infiltration analysis, it was found that immune-related genes were abundant in high-risk groups and had reduced immune status. Conclusion In conclusion, immune checkpoint genes highly associated with disulfidptosis contribute to tumor immunity and can be used to evaluate HCC prognosis. When it comes to predicting overall survival (OS) time in HCC, risk score has been set to be a separate predictor. Through immune cell infiltration analysis, it was found that immune-related genes were abundant in high-risk groups and had reduced immune status. It is possible to measure the prognosis of HCC based on immune checkpoints genes strongly linked to disulfidptosis.

Identifying disulfidptosis subtypes in hepatocellular carcinoma through machine learning and preliminary exploration of its connection with immunotherapy

“…Lastly, we validated the clinical application value of the constructed disulfS signature in our own cohort. Although several studies have attempted to establish a prognostic signature for disulfide death-related genes in HCC [ 16 – 19 , 61 , 62 ], they have primarily focused on bioinformatics analysis without conducting further molecular biology experiments to confirm the existence of disulfide death in hepatocellular carcinoma. Additionally, some of these studies constructed prognostic models with inadequate AUC values for ROC curves in validation cohorts, failing to validate the predictive effects of these models in real-world settings.…”

Disulfidptosis decoded: a journey through cell death mysteries, regulatory networks, disease paradigms and future directions

“…1.liver cancer: SPP1, MYBL2 [ 18 ]; SLC7A11 [ 19 , 20 ]; LRPPRC [ 20 ]; TNFRSF14, TNFRSF4, TNFSF4 [ 21 ], BTN2A1, BTN2A2 [ 21 ]; SLCO1B1 [ 22 ]…”

“…Furthermore, studies indicate that disulfidptosis-related genes, specifically SLC7A11 and LRPPRC, could potentially serve as independent prognostic factors for HCC [ 20 ]. Immune checkpoint genes, such as TNFRSF14, TNFRSF4, TNFSF4, BTN2A1, and BTN2A2,are suggested to have a strong correlation with disulfidptosis and may play an important role in enhancing tumor immunity, potentially making them useful indicators for predicting the prognosis of HCC [ 21 ]. In vitro experiments have shown that the overexpression of the disulfidptosis-related glycolysis gene SLCO1B1 effectively inhibits the proliferation, migration, and invasion of HCC cells.…”

Disulfidptosis: A new type of cell death

“…Recent studies have suggested that disulfidptosis plays a significant role in the onset and progression of various diseases. Associations have been observed with cancer [2,5,6], neurodegenerative diseases [7,8], cardiovascular diseases [9], and liver diseases [10][11][12], and other conditions are closely related to disulfidptosis [13][14][15].…”