Disulfidptosis-related genes of prognostic signature and immune infiltration features in hepatocellular carcinoma supported by bulk and single-cell RNA sequencing data

Yuyang Wang; Zibo Yuan; Qingwei Zhu; Jun Ma; Qiliang Lu; Zunqiang Xiao

doi:10.21037/jgo-23-949

Disulfidptosis-related genes of prognostic signature and immune infiltration features in hepatocellular carcinoma supported by bulk and single-cell RNA sequencing data

J Gastrointest Oncol. 2024 Feb 29;15(1):377-396. doi: 10.21037/jgo-23-949. Epub 2024 Feb 1.

Authors

Yuyang Wang^#¹, Zibo Yuan^#¹, Qingwei Zhu¹, Jun Ma², Qiliang Lu², Zunqiang Xiao³

Affiliations

¹ Qingdao Medical College, Qingdao University, Qingdao, China.
² General Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, China.
³ General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, China.

^# Contributed equally.

Abstract

Background: Disulfidptosis is a new type of cellular death triggered in response to disulfide stress and is strongly linked to the progression of malignancies. Hepatocellular carcinoma (HCC) is a very common malignancy. Some reports have suggested a link between disulfidptosis-related genes (DRGs) and cancer; however, further research needs to be conducted.

Methods: In this study, HCC data from the Cancer Genome Atlas-Liver Hepatocellular Carcinoma and Gene Expression Omnibus data sets were collected and analyzed. A univariate Cox regression analysis, least absolute shrinkage and selection operator, and multivariate Cox regression analysis were conducted to identify the hub DRGs signature for prognosis. The HCC patients were allocated to high- and low-risk groups based on their disulfidptosis risk scores. The model was validated with a high degree of precision using both internal and external validation data sets. "ESTIMATE" and "CIBERSORT" packages were employed to assess the immunological landscapes and immune cell infiltration. The IMvigor210 cohort was chosen to validate the immunotherapy results. A drug sensitivity analysis was conducted to identify targeted medications. The expression of the hub DRGs in the HCC cells was confirmed using cytological techniques.

Results: The bioinformatic analysis revealed that 16 genes showed differential expression. A prognostic model was developed based on four genes: RPN1, SLC2A1, SLC2A4, and SLC7A11. A notable difference in prognosis was observed between the two risk groups. Based on the results of the immune microenvironment, tumor mutation burden, immunotherapy, and drug screening analyses, the DRGs signature can be employed in HCC immunotherapy decision making. Further, the expression levels of the hub DRGs were significantly upregulated in the HCC cells.

Conclusions: Our four-DRGs signature could be used to predict HCC prognosis. Further, this study showed that the hub DRGs could serve as biomarkers for immunotherapy prediction and could potentially guide targeted therapies.

Keywords: Disulfidptosis; drug sensitivity; immune checkpoints; immune microenvironment.