A Novel Ferroptosis-related Gene Signature for Overall Survival Prediction in Patients with Hepatocellular Carcinoma

et al. 2020

Front. Cell Dev. Biol.

100

BackgroundImmunotherapy and sorafenib exert anti-tumor effects via ferroptosis, but reliable biomarkers for the individual treatment and prognosis prediction of hepatocellular carcinoma (HCC) based on the ferroptosis and immune status remain lacking.MethodsFerroptosis-related genes (FRGs) were identified by downloading data from FerrDb and by searching and reading original articles from PubMed. Immune-related genes (IRGs) were downloaded from ImmPort. Prognostic FRGs and IRGs in the GSE14520 (n = 220) and The Cancer Genome Atlas (TCGA, n = 365) datasets were identified. Least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used for model construction. Ferroptosis expression profiles, the infiltration of immune cells, and the somatic mutation status were analyzed and compared.ResultsTwenty-seven prognostic ferroptosis- and immune-related signatures were included to construct a comprehensive index of ferroptosis and immune status (CIFI). A subgroup of patients was identified as having a high CIFI value, which was associated with a worse prognosis. This subgroup of patients had significantly up-regulated expressions of many suppressors of ferroptosis and higher fractions of immunosuppressive cells, such as cancer-associated fibroblasts (CAFs) and myeloid-derived suppressor cells (MDSCs). Notably, somatic mutation analysis indicated that high-CIFI patients had higher levels of tumor heterogeneity and higher mutation frequencies of genes like TP53.ConclusionIn this work, a novel prognostic classifier was developed based on ferroptosis- and IRGs in HCC, and this classifier could be used for prognostic prediction and the selection of patients for immunotherapies and targeted therapies.

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Combined Ferroptosis and Immune Prognostic Classifier for Hepatocellular Carcinoma

Liu

et al. 2020

Front. Cell Dev. Biol.

100

“…Recently, we found three studies that have reported ferroptosis gene signatures. These three studies focused on HCC [50], clear cell renal cell carcinoma [51], and glioma [52]. There are some similarities between our research and these three articles.…”

Section: Discussionmentioning

confidence: 62%

A Ferroptosis-associated Gene Signature for the Prediction of Prognosis and Therapeutic Response in Luminal-type Breast Carcinoma

Peng

et al. 2020

Preprint

Background: Ferroptosis is a new form of regulated cell death (RCD), and its emergence has provided a new approach to the progression and drug resistance of breast cancer (BRCA). However, there is still a great gap in the study of ferroptosis-related genes in BRCA, especially luminal-type BRCA patients.Methods: We downloaded the mRNA expression profiles and corresponding clinical data of BRCA patients from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) databases. Then, we built a prognostic multigene signature with ferroptosis-related differentially expressed genes (DEGs) in the METABRIC cohort and validated it in the TCGA cohort. The predictive value of this signature was investigated in terms of mutations, copy number variations (CNVs), the immune microenvironment, tumor purity, related pathway and the probability of a response to immunotherapy and chemotherapy.Findings: The patients were divided into a high-risk group and a low-risk group by the ferroptosis-associated gene signature, and the high-risk group had a worse overall survival (OS). The risk score based on the 10 ferroptosis-related gene-based signature was determined to be an independent prognostic predictor in both the METABRIC and TCGA cohorts (HR, 1.41, 95% CI, 1.14-1.76, P = 0.002; HR, 2.19, 95% CI, 1.13-4.26, P= 0.02). Gene set enrichment analysis indicated that the term “cytokine-cytokine receptor interaction” was enriched in the high risk score subgroup. Moreover, the immune infiltration scores of most immune cells were significantly different between the two groups, and the low-risk group was much more sensitive to immunotherapy and chemotherapy. In addition, we found that amplifications on chromosome 12 accompanied by the deletion of chromosome 21 were enriched in the high-risk subgroup. Pathway score results suggest that the ferroptosis-related gene-based signature show differences in most breast cancer-associated phenotypes. Finally, a nomogram incorporating a classifier based on the 10 ferroptosis-related genes, tumor stage, age and histologic grade was established. This nomogram showed a favorable discriminating ability and might contribute to clinical decision-making for luminal-type breast carcinoma.

“…However, there are no reports on that prognostic model of lncRNA related to ferroptosis was constructed. Although two previous genetic prognostic models of ferroptosis have been reported in hepatocellular carcinoma [37] and glioma [38], our study is the rst to report the study of ferroptosis-related lncRNA prognostic models in LAUD…”

Section: Discussionmentioning

confidence: 95%

Identification of a nine ferroptosis-related lncRNA prognostic signature for lung adenocarcinoma

Tong¹,

Yang

et al. 2021

Preprint

Background Recently, mounting of studies has shown that lncRNA affects tumor progression through the regulation of ferroptosis. The current study aims to construct a robust ferroptosis-related lncRNAs signature to increase the predicted value of lung adenocarcinoma (LUAD) by bioinformatics analysis. Methods The transcriptome data were abstracted from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were screened by comparing 535 LAUD tissues with 59 adjacent non-LAUD tissues. Univariate Cox regression, lasso regression, multivariate Cox regression were conducted to design a ferroptosis-related lncRNA signature. This signature’s prognosis was verified by the log-rank test of Kaplan-Meier curve and the area under curve (AUC) of receiver operating characteristic (ROC) in train set, test set, and entire set. Furthermore, univariate and multivariate Cox regression were used to analyze its independent prognostic ability. The relationship of the ferroptosis-linked lncRNAs' expression and clinical variables was demonstrated by Wilcoxon rank-sum test and Kruskal-Wallis test. Gene set enrichment analysis (GSEA) was performed to signaling pathways it may involve. Results 1224 differentially expressed lncRNAs were idendified, of which 195 are ferroptosis-related lncRNAs. A nine ferroptosis-related lncRNAs (AC099850.3, NAALADL2-AS2, AL844908.1, AL365181.2, SMIM25, FAM83A-AS1, LINC01116, AL049836.1, C20orf197) prognostic signature was constucted. This model's prognosis in the high-risk group is obviously worse than that of the low-risk group in train set, test set, and entire set. The AUC of ROC predicting the three years survival in the train set, test set, and entire set was 0.754, 0.716, and 0.738, respectively. Moreover, the designed molecular signature was found to be an independent prognostic variable. The expression of these lncRNAs and the lncRNA signature are related to clinical stage, T stage, Lymph-node status, distant metastasis. Finally, GSEA analysis results show that the signature is involved in eight tumor-related and metabolism-related signaling pathways Conclusion The current study constructed, validated, and evaluated a nine ferroptosis-related lncRNA signature which can independently be used to predict the prognosis of LAUD patients, and may become a new therapeutic target.