Author:
Chen Xuenuo,Wang Zhijian,Wu Yilin,Lan Yinghua,Li Yongguo
Abstract
IntroductionHepatocellular carcinoma (HCC) is the most common type of cancer worldwide and is a major public health problem in the 21st century. Disulfidopathy, a novel cystine-associated programmed cell death, plays complex roles in various tumors. However, the relationship between disulfidoptosis and prognosis in patients with HCC remains unclear. This study aimed to explore the relationship between disulfideptosis and the prognosis of liver cancer and to develop a prognostic model based on amino acid metabolism and disulfideptosis genes.MethodsWe downloaded the clinicopathological information and gene expression data of patients with HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and classified them into different molecular subtypes based on the expression patterns of disulfidoptosis-associated amino acid metabolism genes (DRAGs). Patients were then classified into different gene subtypes using the differential genes between the molecular subtypes, and the predictive value of staging was assessed using survival and clinicopathological analyses. Subsequently, risk prognosis models were constructed based on Cox regression analysis to assess patient prognosis, receiver operating characteristic (ROC) curves, somatic mutations, microsatellite instability, tumor microenvironment, and sensitivity to antitumor therapeutic agents.ResultsPatients were classified into two subtypes based on differential DRAGs gene expression, with cluster B having a better survival outcome than cluster A. Three gene subtypes were identified based on the differential genes between the two DRAGs molecular subtypes. The patients in cluster B had the best prognosis, whereas those in cluster C had the worst prognosis. The heat map showed better consistency in the patient subtypes obtained using both typing methods. We screened six valuable genes and constructed a prognostic signature. By scoring, we found that patients in the low-risk group had a better prognosis, higher immune scores, and more abundant immune-related pathways compared to the high-risk group, which was consistent with the tumor subtype results.DiscussionIn conclusion, we developed a prognostic signature of disulfidptosis-related amino acid metabolism genes to assist clinicians in predicting the survival of patients with HCC and provide a reference value for targeted therapy and immunotherapy for HCC.
Reference38 articles.
1. Hepatocellular carcinoma;Villanueva;N Engl J Med,2019
2. A global view of hepatocellular carcinoma: trends, risk, prevention and management;Yang;Nat Rev Gastroenterol Hepatol,2019
3. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017;Zhou;Lancet,2019
4. Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer;Liu;Nat Cell Biol,2020
5. Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy;Koppula;Protein Cell,2021
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献