Differences of ferroptosis-related genes between White and Asian patients with liver cancer
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ABSTRACT:
SUBMITTER: Xia P
PROVIDER: S-EPMC10492120 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: Several reports suggest that vascular endothelial growth factor (VEGF)-targeted therapy in metastatic renal cell carcinoma (mRCC) may be more toxic in Asian vs non-Asian populations. Comparative efficacy of these agents with respect to ethnicity is not well characterised. METHODS: A multicentre, retrospective, cohort study using Asian and non-Asian centres which collected data on ethnicity, dose reductions and outcomes using the International mRCC Database Consortium. RESULTS: This study included 1024 (464 Asian, 560 non-Asian) patients with a 29.4 months median follow-up. The percentage of dose modifications/reductions between non-Asians and Asians was similar (55% vs 61% P=0.1197). When adjusted for risk groups, there was no difference in overall or progression-free survival between non-Asians and Asians. Patients with dose reductions due to toxicity had longer treatment durations and overall survival than those who did not in both non-Asian (10.6 vs 5.0 months, P<0.0001; 22.6 vs 16.1 months, P=0.0016, respectively) and Asian populations (8.9 vs 5.4 months, P=0.0028; 28.0 vs 18.7 months, P=0.0069, respectively). CONCLUSIONS: Adjusting for risk groups, there appears to be no difference in outcome between Asian vs non-Asian patients with mRCC treated with VEGF-targeted therapy. Judicious dose reductions may allow for better outcomes in both populations due to longer treatment durations, but direct comparisons are needed.
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Project description:Different ethnic groups have different incidence rate of hepatocellular carcinoma (HCC). In addition to lifestyle and environmental factors, genetic susceptibility is also an important reason. In this study, we screened the immune related genes and stromal related genes in White and Asian liver cancer patients cohort of The Cancer Genome Atlas (TCGA) the using ESTIMATE algorithm. Hub genes that significantly associated with overall survival (OS) were selected from White and Asian liver cancer patients, respectively. In addition, we validated the functions of two hub genes, IL-18RAP and GPM6A, in vivo and in vitro. We confirmed different races have different tumor immune microenvironments. Immune microenvironment can influence and change the efficacy of immunotherapy for liver cancer patients.
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Project description:The drug response sensitivity and related prognosis of prostate cancer varied from races, while the original mechanism remains rarely understood. In this study, the comprehensive signature including transcriptomics, epigenome and single nucleotide polymorphisms (SNPs) of 485 PCa cases- including 415 Whites, 58 Blacks and 12 Asians from the TCGA database were analyzed to investigate the drug metabolism differences between races. We found that Blacks and Whites had a more prominent drug metabolism, cytotoxic therapy resistance, and endocrine therapy resistance than Asians, while Whites were more prominent in drug metabolism, cytotoxic therapy resistance and endocrine therapy resistance than Blacks. Subsequently, the targeted regulation analysis indicated that the racial differences in cytotoxic therapy resistance, endocrine therapy resistance, might originate from drug metabolisms, and 19 drug metabolism-related core genes were confirmed in the multi-omics network for subsequent analysis. Furthermore, we verified that CYP1A1, CYP3A4, CYP2B6, UGT2B17, UGT2B7, UGT1A8, UGT2B11, GAS5, SNHG6, XIST significantly affected antineoplastic drugs sensitivities in PCa cell lines, and these genes also showed good predictive efficiency of drug response and treatment outcomes for PCa in this cohort of patients. These findings revealed a comprehensive signature of drug metabolism differences for the Whites, Blacks and Asians, and it may provide some evidence for making individualized treatment strategies.
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Project description:To seek ferroptosis related genes in liver cancer cells, we treated HepG2 cells using ferroptosis inducer Erastin and inhibitor Ferrostatin, respectively. We found that a subset of genes were up-regulated in Erastin treatment groups and down-regulated in Ferrostatin treatment groups, suggesting that these genes might be correlated with ferroptosis.
2019-06-10 | GSE104462 | GEO
Project description:Esophageal cancer is a common cancer worldwide and has a poor prognosis. The incidence of esophageal squamous cell cancer has been decreasing, whereas the incidence of esophageal adenocarcinoma has been increasing rapidly, particularly in Western men. Squamous cell cancer continues to be the major type of esophageal cancer in Asia, and the main risk factors include tobacco smoking, alcohol consumption, hot beverage drinking, and poor nutrition. In contrast, esophageal adenocarcinoma predominately affects the whites, and the risk factors include smoking, obesity, and gastroesophageal reflux disease. In addition, Asians and Caucasians may have different susceptibilities to esophageal cancer due to different heritage backgrounds. However, comparison studies between these two populations are limited and need to be addressed in the near future. Ethnic differences should be taken into account in preventive and clinical practices.
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Project description:Genome-wide analysis of ferroptosis related genes in liver cancer cells.
| PRJNA412671 | ENA
Project description:BackgroundThe prevalence of lung adenocarcinomas (LUADs) has dramatically increased in recent decades. Ferroptosis is a process of iron-dependent regulatory cell death. It is still unclear whether the expression of ferroptosis-related genes (FRGs) is involved in the pathogenesis and survival of patients with LUAD.MethodsWe retrieved LUAD data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and used LASSO Cox regression analysis to select the gene signature suitable for modeling. The risk score was calculated according to the model, and the patients were divided into high- and low-risk groups according to the median risk score. Functional enrichment analysis was carried out by this group, and a model for predicting clinical prognosis was established by combining this group with clinical factors.ResultsGene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) analysis showed that there were several immune-related pathways and immune infiltration differences between high- and low-risk groups. A prognostic model integrating 10 ferroptosis-related genes (FR-DEGs), and clinical factors were constructed and validated in an external cohort.ConclusionsThe FR-DEGs signature was related to immune infiltration, and a model based on FR-DEGs and clinical factors was established to predict the prognosis of patients with LUAD.
| S-EPMC8201541 | biostudies-literature
Project description:Ferroptosis is a new type of programmed cell death, which occurs with iron dependence. Previous studies have showed that ferroptosis plays an important regulatory role in the occurrence and development of tumors. Colon cancer is one of the major morbidities and causes of mortality in the world. This study used RNA-seq and colon cancer clinical data to explore the relationship between ferroptosis-related genes and colon cancer. Based on the fifteen prognostic ferroptosis-related genes, two molecular subgroups of colon cancer were identified. Surprisingly, we also found cluster2 was characterized by lower mutation burden and expression of checkpoint genes, better survival, and higher expression of NOX1. Moreover, cluster2 has fewer BRAF mutations. We also found the expression of NOX1 is related to the status of BRAF. Finally, using 15 ferroptosis-related genes from The Cancer Genome Atlas cohort, we constructed a prognosis model, and this model may be used to predict the prognosis of patients in clinics.
| S-EPMC8199073 | biostudies-literature
Project description:BackgroundThe prognosis of patients with breast cancer (BRCA) is difficult to predict because of the high degree of heterogeneity and complex etiological factors. Ferroptosis, an iron-dependent, new form of cell death, plays an important role in regulation of tumor growth and progression. The aim of this study was to clarify the predictive value of ferroptosis-related genes in the overall survival of patients with BRCA.MethodsThe messenger RNA expression profile and clinical information of patients with BRCA were collected from The Cancer Genome Atlas (TCGA) database. The differences between BRCA and adjacent normal tissues were analyzed, and candidates with differentially expressed ferroptosis-related genes were identified. Through Cox and LASSO analyses, the prognostic genetic characteristics of ferroptosis-related genes were established. Lastly, according to the median risk score, the patients were divided into high-risk and low-risk groups, a nomogram was constructed, and the prediction accuracy was tested.ResultsIt was determined that the four ferroptosis related genes had a significant difference in survival in BRCA (P<0.05); a prognostic model was constructed based on the four ferroptosis related genes, and the overall survival of patients in the high-risk group was significantly worse (P<0.05). The four-gene nomogram can quantify the contribution of each index to survival, and the calibration chart shows high prediction accuracy.ConclusionsThis study constructed four ferroptosis related gene characteristics and nomogram, which can effectively predict the prognosis of BRCA patients and provide new insights for future anti-cancer treatments based on ferroptosis targets.
| S-EPMC9372208 | biostudies-literature
Project description:BackgroundFerroptosis is widely involved in the occurrence and development of various cancers, but a specific mechanism involving ferroptosis in cervical cancer is still unclear.MethodsBased on the expressions of ferroptosis-related genes, a prognostic model was constructed using lasso regression, and the overall predictive performance of this model was verified. An in-depth analysis of the prognostic model was then conducted.ResultsThe prognostic model showed good predictive performance in both the validation and test sets. Mechanism analysis indicated that differences in the tumor microenvironment were the basis of the predictive ability of the model. Notably, CA9 mRNA was significantly overexpressed in cervical carcinoma, tissues but not in normal cervix tissues. A pair of ceRNAs (CA9/ULBP2) could be involved in the carcinogenesis and development of cervical cancer, and the potential target might be hsa-miR-34a. In addition, predicted miRNAs and drugs for these DEGs were identified.ConclusionsWe constructed a prognostic model with good predictive performance, based on the expression of ferroptosis-related genes. Further research found that the ceRNA pairs of ULBP2/CA9 could regulate cervical cancer through hsa-miR-34a. These results identified the mechanism of ferroptosis in cervical cancer, and might provide novel therapeutics for cervical cancer patients.
| S-EPMC9614331 | biostudies-literature