Identification of the Ferroptosis-Associated Gene Signature to Predict the Prognostic Status of Endometrial Carcinoma Patients

Qin, Jinlong; Shao, Xiaowen; Wu, Lei; Du, Hongling

doi:10.1155/2021/9954370

Cited by 9 publications

(8 citation statements)

References 53 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, we validated the performance differences between our signature and other previously reported gene signatures in EC. The AUC of present protein signature for 1, 3 and 5 year OS prediction was higher in comparison with Hu's signature [ 23 ], Huang's signature [ 24 ], Liu's signature [ 25 ] and Qin's signature [ 26 ] (Fig. S 3 a).…”

Section: Resultsmentioning

confidence: 99%

Protein-based prognostic signature for predicting the survival and immunotherapeutic efficiency of endometrial carcinoma

Lai

Yang

2022

BMC Cancer

View full text Add to dashboard Cite

Background Endometrial cancer (EC) is the most frequent malignancy of the female genital tract worldwide. Our study aimed to construct an effective protein prognostic signature to predict prognosis and immunotherapy responsiveness in patients with endometrial carcinoma. Methods Protein expression data, RNA expression profile data and mutation data were obtained from The Cancer Proteome Atlas (TCPA) and The Cancer Genome Atlas (TCGA). Prognosis-related proteins in EC patients were screened by univariate Cox regression analysis. Least absolute shrinkage and selection operator (LASSO) analysis and multivariate Cox regression analysis were performed to establish the protein-based prognostic signature. The CIBERSORT algorithm was used to quantify the proportions of immune cells in a mixed cell population. The Immune Cell Abundance Identifier (ImmuCellAI) and The Cancer Immunome Atlas (TCIA) web tools were used to predict the response to immunochemotherapy. The pRRophetic algorithm was used to estimate the sensitivity of chemotherapeutic and targeted agents. Results We constructed a prognostic signature based on 9 prognostic proteins, which could divide patients into high-risk and low-risk groups with distinct prognoses. A novel prognostic nomogram was established based on the prognostic signature and clinicopathological parameters to predict 1, 3 and 5-year overall survival for EC patients. The results obtained with Clinical Proteomic Tumor Analysis Consortium (CPTAC), Human Protein Atlas (HPA) and immunohistochemical (IHC) staining data from EC samples in our hospital supported the predictive ability of these proteins in EC tumors. Next, the CIBERSORT algorithm was used to estimate the proportions of 22 immune cell types. The proportions of CD8 T cells, T follicular helper cells and regulatory T cells were higher in the low-risk group. Moreover, we found that the prognostic signature was positively associated with high tumor mutation burden (TMB) and high microsatellite instability (MSI-H) status in EC patients. Finally, ImmuCellAI and TCIA analyses showed that patients in the low-risk group were more inclined to respond to immunotherapy than patients in the high-risk group. In addition, drug sensitivity analysis indicated that our signature had potential predictive value for chemotherapeutics and targeted therapy. Conclusion Our study constructed a novel prognostic protein signature with robust predictive ability for survival and efficiency in predicting the response to immunotherapy, chemotherapy and targeted therapy. This protein signature represents a promising predictor of prognosis and response to cancer treatment in EC patients.

show abstract

Section: Resultsmentioning

confidence: 99%

Protein-based prognostic signature for predicting the survival and immunotherapeutic efficiency of endometrial carcinoma

Lai

Yang

2022

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…Besides the MAPK signaling, our results highlighted the involvement of ERK signaling in ferroptosis targeted by GSH. ERK signaling is associated with ferroptosis in many cancers, including multiple myeloma ( Chen J. et al, 2021 ), endometrial carcinoma ( Qin et al, 2021 ), hepatocellular carcinoma ( Fei et al, 2021 ), and pancreatic cancer ( Ye et al, 2020 ). Specifically, the ERK signaling pathway has been linked with ferroptosis and associated with the prognosis of OC ( Chen R. et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology Identifies Therapeutic Targets and the Mechanisms of Glutathione Action in Ferroptosis Occurring in Oral Cancer

Huang

Zhan

2022

Front. Pharmacol.

View full text Add to dashboard Cite

Oral cancer (OC) is one of the most pernicious cancers with increasing incidence and mortality worldwide. Surgery is the primary approach for the treatment of early-stage OC, which reduces the quality of life of the patients. Therefore, there is an urgent need to discover novel treatments for OC. Targeting ferroptosis to induce cell death through the modulation of lipid oxidation has been used as a new approach to treat many cancers. Glutathione (GSH) is a coenzyme factor of GSH peroxidase 4, and it carries potential applicability in treating OC. By using network pharmacology and molecular docking followed by systematic bioinformatic analysis, we aimed to study GSH-targeting ferroptosis to treat OC. We identified 14 core molecular targets, namely, EGFR, PTGS2, HIF1A, VEGFA, TFRC, SLC2A1, CAV1, CDKN2A, SLC3A2, IFNG, NOX4, DDIT4, CA9, and DUSP1, involved in ferroptosis that were targeted by GSH for OC treatment. Functional characterization of these molecular targets showed their importance in the control of cell apoptosis, cell proliferation, and immune responses through various kinase activities such as the mitogen-activated protein kinase activity (e.g., ERK1 and ERK2 cascades) and modulation of TOR signaling (e.g., the HIF-1 signaling pathway). Molecular docking further revealed the direct binding of GSH with EGFR, PTGS2, and HIF1A proteins. These findings provide a novel insight into the targets of GSH in ferroptosis as well as possible molecular mechanisms involved, suggesting the possible use of GSH as a combined therapy for treating OC.

show abstract

“…It is also involved in the production of aromatase substrate in breast cancer ( 36 ). SAT1 is a transcriptional target of p53 in human melanoma and lung cancer cell lines ( 37 ), and can sensitize cells to ferroptosis and inhibit tumor growth ( 38 ). Additionally, overexpressing SAT1 was reported to lead to mitochondria-mediated apoptosis in mammalian cells ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis-related gene signature predicts prognosis in kidney renal papillary cell carcinoma

Yin¹,

Mei²,

Liang³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

Ferroptosis, an iron-dependent form of selective cell death, is involved in the development of many cancers. However, the role of ferroptosis-related genes (FRGs) in kidney renal papillary cell carcinoma (KIRP) is unclear. In this study, we examined the mRNA expression profiles and clinical data of patients with KIRP from the TCGA cohort. Consequently, 41 differentially-expressed FRGs were screened using the limma package, and 17 prognostic-related FRGs were identified by survival analysis and univariate Cox regression analyses. Thereafter, a ferroptosis-related gene prognostic index (FRGPI) was constructed based on five FRGs (AKR1C3, SAT1, FANCD2, HSBP1 and SQLE), using lasso Cox and multivariate Cox regression analyses. KIRP patients with high FRGPI scores displayed worse outcomes. Furthermore, the FRGPI was shown to be a reliable independent prognostic factor in both the training and testing cohorts. Comprehensive analysis also showed that the FRGPI can distinguish gene mutation, functional enrichment of immune cells and molecular function-related pathways. Interestingly, low FRGPI score could be more benefit from immune checkpoint inhibitors (ICIs) therapy. Then, the two hub prognostic genes (AKR1C3 and FANCD2) as a risk gene for KIRP were identified based on the FRGPI module, and the expression profiles of these two genes were validated using human KIRP cells, besides, we furthermore discovered that Fancd2 is significantly up-regulated in most cancers and is associated with prognosis. In conclusion, these findings showed that FRGPI can accurately predict the prognosis of patients with KIRP, suggesting that this risk model is a promising prognostic biomarker for these patients. Moreover, targeting ferroptosis (FANCD2) could be a potential therapeutic alternative for various cancers.

show abstract

Identification of the Ferroptosis-Associated Gene Signature to Predict the Prognostic Status of Endometrial Carcinoma Patients

Cited by 9 publications

References 53 publications

Protein-based prognostic signature for predicting the survival and immunotherapeutic efficiency of endometrial carcinoma

Protein-based prognostic signature for predicting the survival and immunotherapeutic efficiency of endometrial carcinoma

Network Pharmacology Identifies Therapeutic Targets and the Mechanisms of Glutathione Action in Ferroptosis Occurring in Oral Cancer

Ferroptosis-related gene signature predicts prognosis in kidney renal papillary cell carcinoma

Contact Info

Product

Resources

About