A novel signature of the ligand and receptor genes associated with disulfidoptosis for prediction of prognosis, immunologic therapy responses in hepatocellular carcinoma

Chong Fu; Chang Cheng; Yanping Zhang

doi:10.1016/j.heliyon.2023.e19502

A novel signature of the ligand and receptor genes associated with disulfidoptosis for prediction of prognosis, immunologic therapy responses in hepatocellular carcinoma

Heliyon. 2023 Aug 25;9(9):e19502. doi: 10.1016/j.heliyon.2023.e19502. eCollection 2023 Sep.

Authors

Chong Fu¹, Chang Cheng¹, Yanping Zhang¹

Affiliation

¹ Department of Gastroenterology, Anqing Municipal Hospital, 352#, Renmin Road, Anqing, Anhui, 246000, PR China.

Abstract

Backgroud: We aimed to explore the prognostic features of ligand and receptor genes associated with disulfidoptosis in hepatocellular carcinoma (HCC) and establish a risk signature utilizing these genes to predict the prognosis of HCC patients.

Methods: We used scRNA-seq data from GSE166635 to differentiate malignant cells from normal cells using "copykat".The study thoroughly examined the disparities in disulfidoptosis scores and the associated gene expressions between malignant and normal cells.We identified key ligand and receptor genes that are specific to HCC cells.Subsequently, Correlation analysis was conducted to ascertain the ligand and receptor genes associated with disulfidoptosis.We performed univariate Cox regression analysis to identify prognostic ligand and receptor genes associated with disulfidoptosis.We employed LASSO to construct a risk signature using prognostic ligand and receptor genes associated with disulfidoptosis.Lastly, we developed a nomogram model that integrates the risk signature with clinicopathological characteristics.

Results: Malignant cells displayed a marked increase in disulfidoptosis scores and the expression of associated genes compared to normal cells.We identified 110 receptor and ligand genes significantly associated with disulfidoptosis, and narrowed them down to create a risk signature comprising eight genes.Multivariate analysis confirmed the risk signature as an independent prognostic factor for HCC and validated its predictive value for immunotherapy outcomes.A novel nomogram was developed, incorporating stage information and the risk signature derived from disulfidoptosis-related receptor and ligand genes, demonstrating excellent predictive accuracy and reliability in HCC prognosis prediction.

Conclusion: Risk signatures based on disulfidoptosis-associated ligand and receptor genes can effectively predict HCC prognosis and may inform immunotherapy strategies.

Keywords: Bulk RNA sequencing; Disulfidoptosis; Hepatocellular carcinoma; Ligand and receptor genes; Single cell RNA sequencing.