Ferroptosis-related gene signature predicts the prognosis of papillary thyroid carcinoma

Abstract

Background Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC), accounting for more than 80% of all cases. Ferroptosis is a novel iron-dependent and Reactive oxygen species (ROS) reliant type of cell death which is distinct from the apoptosis, necroptosis and pyroptosis. Considerable studies have demonstrated that ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in PTC remains unclear. This study aims at exploring the expression of ferroptosis-related genes (FRG) and their prognostic values in PTC. Methods A ferroptosis-related gene signature was constructed using lasso regression analysis through the PTC datasets of the Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the bioinformatics functions of significantly different genes (SDG) of ferroptosis. Additionally, the correlations of ferroptosis and immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT database. Finally, SDG were test in clinical PTC specimens and normal thyroid tissues. Results LASSO regression model was utilized to establish a novel FRG signature with 10 genes (ANGPTL7, CDKN2A, DPP4, DRD4, ISCU, PGD, SRXN1, TF, TFRC, TXNRD1) to predicts the prognosis of PTC, and the patients were separated into high-risk and low-risk groups by the risk score. The high-risk group had poorer survival than the low-risk group (p < 0.001). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Multivariate regression analysis identified the prognostic signature-based risk score was an independent prognostic indicator for PTC. The functional roles of the DEGs in the TGCA PTC cohort were explored using GO enrichment and KEGG pathway analyses. Immune related analysis demonstrated that the most types of immune cells and immunological function in the high-risk group were significant different with those in the low-risk group. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) verified the SDG have differences in expression between tumor tissue and normal thyroid tissue. In addition, cell experiments were conducted to observe the changes in cell morphology and expression of signature’s genes with the influence of ferroptosis induced by sorafenib. Conclusions We identified differently expressed FRG that may involve in PTC. A ferroptosis-related gene signature has significant values in predicting the patients’ prognoses and targeting ferroptosis may be an alternative for PTC’s therapy.

A Potential Four-Gene Signature and Nomogram for Predicting the Overall Survival of Papillary Thyroid Cancer

“…To understand the potential mechanisms affecting the prognosis of patients with PTC, immune analysis, GSEA, and GSVA were performed between good-prognosis and poor-prognosis groups. Surprisingly, in contrast to some other prior studies [ 46 ], immune infiltration and immune microenvironment displayed little effect on the OS of PTC patients. These results can be explained, in part, by the fact that the four key genes we identified in this study are not directly involved in the process of tumor immunity.…”

Construction and validation of a novel Ferroptosis-related gene signature predictive model in rectal Cancer

“…We look forward to further discussion and promotion of the detailed mechanism of this model. In recent years, many clinical prognostic models have been built, involving various cancers and mechanisms [ 21 , 64 – 66 ]. While the model presented in this study is still in its theoretical exploration stage, we hope that through this limited research it will provide a reference for more in-depth research on the mechanism of ferroptosis in the RC field in the future.…”

CDKN2A-mediated molecular subtypes characterize the hallmarks of tumor microenvironment and guide precision medicine in triple-negative breast cancer

“…The expression of this gene is verified to cause cell cycle arrested in the G1 phase, inhibit cell proliferation, promote tumor cell apoptosis, and increase tumor cell chemotherapy sensitivity ( 6 ). Recent studies have pointed out that CDKN2A is correlated with ferroptosis ( 7 ) and cuproptosis ( 8 ) (FAC), which are both novel types of regulated cell death that their occurrence was ion-dependent. Ferroptosis indicates an oxidative cell death resulting from the deterioration of antioxidant function and accretion of lipid reactive oxygen species (ROS) ( 9 ).…”