Identification of a Novel Five Ferroptosis-related Gene Signature As a Promising Prognostic Model for Breast Cancer

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2023 Sep 20

PMID 37728703

Authors

Tian- Cheng Cheng

Jia-Hao Wu

Bei Zhu

Hai-Yan Gao

Lin Zheng

Wei-Xian Chen

Affiliations

Soon will be listed here.

Abstract

Background: Breast cancer (BCa) is a major challenge for women's health worldwide. Ferroptosis is closely related to tumorigenesis and cancer progression. However, the prognostic value of ferroptosis-related genes in BCa remains unclear, and more accurate prognostic models are urgently needed.

Methods: Gene expression profiles and clinical information of BCa patients were collected from public databases. LASSO and multivariate Cox regression analysis were utilized to construct the prognostic gene signature. Kaplan-Meier plotter, receiver operating characteristic (ROC) curves, and nomogram were used to validate the prognostic value of the gene signature. Gene set enrichment analysis was performed to explore the molecular functions and signaling pathways.

Results: Differentially expressed ferroptosis-related genes between BCa samples and normal tissues were obtained. A novel five-gene signature including BCL2, SLC40A1, TFF1, APOOL, and PRAME was established for prognosis prediction. Patients stratified into high-risk or low-risk group displayed significantly different survival. Kaplan-Meier and ROC curves showed a good performance for survival prediction in different cohorts. Biological function analysis revealed that the five-gene signature was associated with cancer progression, immune infiltration, immune response, and drug resistance. Nomogram including the five-gene signature was established.

Conclusion: A novel five ferroptosis-related gene signature and nomogram could be used for prognostic prediction in BCa.

Citing Articles

Wang Z, Li J, Wang F, Cheng C, Wu X, Guo W Sci Rep. 2024; 14(1):27477.

PMID: 39523404 PMC: 11551150. DOI: 10.1038/s41598-024-77389-4.

PRAME Updated: Diagnostic, Prognostic, and Therapeutic Role in Skin Cancer.

Cassalia F, Danese A, Tudurachi I, Federico S, Zambello A, Guidotti A Int J Mol Sci. 2024; 25(3).

PMID: 38338862 PMC: 10855739. DOI: 10.3390/ijms25031582.

References

Feng Z, Chen P, Li K, Lou J, Wu Y, Li T . A Novel Ferroptosis-Related Gene Signature Predicts Recurrence in Patients With Pancreatic Ductal Adenocarcinoma. Front Mol Biosci. 2021; 8:650264. PMC: 8495121. DOI: 10.3389/fmolb.2021.650264. View

Liu H, Hu H, Li G, Zhang Y, Wu F, Liu X . Ferroptosis-Related Gene Signature Predicts Glioma Cell Death and Glioma Patient Progression. Front Cell Dev Biol. 2020; 8:538. PMC: 7363771. DOI: 10.3389/fcell.2020.00538. View

Wang D, Wei G, Ma J, Cheng S, Jia L, Song X . Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients. BMC Cancer. 2021; 21(1):645. PMC: 8165796. DOI: 10.1186/s12885-021-08341-2. View

Giaquinto A, Sung H, Miller K, Kramer J, Newman L, Minihan A . Breast Cancer Statistics, 2022. CA Cancer J Clin. 2022; 72(6):524-541. DOI: 10.3322/caac.21754. View

Xu P, Ge F, Li W, Xu Z, Wang X, Shen J . MicroRNA-147a Targets SLC40A1 to Induce Ferroptosis in Human Glioblastoma. Anal Cell Pathol (Amst). 2022; 2022:2843990. PMC: 9356897. DOI: 10.1155/2022/2843990. View

Zhang X, Wu H, Niu J, Hu Y, Zhang W, Chang J . A novel mitochondria-related gene signature in esophageal carcinoma: prognostic, immune, and therapeutic features. Funct Integr Genomics. 2023; 23(2):109. DOI: 10.1007/s10142-023-01030-2. View

Stockwell B, Friedmann Angeli J, Bayir H, Bush A, Conrad M, Dixon S . Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell. 2017; 171(2):273-285. PMC: 5685180. DOI: 10.1016/j.cell.2017.09.021. View

Wu M, Zhang X, Zhang W, Chiou Y, Qian W, Liu X . Cancer stem cell regulated phenotypic plasticity protects metastasized cancer cells from ferroptosis. Nat Commun. 2022; 13(1):1371. PMC: 8927306. DOI: 10.1038/s41467-022-29018-9. View

Duffy M, Walsh S, McDermott E, Crown J . Biomarkers in Breast Cancer: Where Are We and Where Are We Going?. Adv Clin Chem. 2015; 71:1-23. DOI: 10.1016/bs.acc.2015.05.001. View

10.

Al-Khadairi G, Naik A, Thomas R, Al-Sulaiti B, Rizly S, Decock J . PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer. J Transl Med. 2019; 17(1):9. PMC: 6317205. DOI: 10.1186/s12967-018-1757-3. View

11.

Smid M, Wang Y, Klijn J, Sieuwerts A, Zhang Y, Atkins D . Genes associated with breast cancer metastatic to bone. J Clin Oncol. 2006; 24(15):2261-7. DOI: 10.1200/JCO.2005.03.8802. View

12.

Doolan P, Clynes M, Kennedy S, Mehta J, Crown J, ODriscoll L . Prevalence and prognostic and predictive relevance of PRAME in breast cancer. Breast Cancer Res Treat. 2007; 109(2):359-65. DOI: 10.1007/s10549-007-9643-3. View

13.

Christofides A, Konstantinidou E, Jani C, Boussiotis V . The role of peroxisome proliferator-activated receptors (PPAR) in immune responses. Metabolism. 2020; 114:154338. PMC: 7736084. DOI: 10.1016/j.metabol.2020.154338. View

14.

Wang N, Gu Y, Li L, Chi J, Liu X, Xiong Y . Identification of novel prognostic risk signature of breast cancer based on ferroptosis-related genes. Sci Rep. 2022; 12(1):13766. PMC: 9374692. DOI: 10.1038/s41598-022-18044-8. View

15.

Deng S, Zheng Y, Mo Y, Xu X, Li Y, Zhang Y . Ferroptosis Suppressive Genes Correlate with Immunosuppression in Glioblastoma. World Neurosurg. 2021; 152:e436-e448. DOI: 10.1016/j.wneu.2021.05.098. View

16.

. Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma. Cell. 2017; 169(7):1327-1341.e23. PMC: 5680778. DOI: 10.1016/j.cell.2017.05.046. View

17.

Buache E, Etique N, Alpy F, Stoll I, Muckensturm M, Reina-San-Martin B . Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice. Oncogene. 2011; 30(29):3261-73. PMC: 3141110. DOI: 10.1038/onc.2011.41. View

18.

Liu G, Zeng H, Zhang C, Xu J . Identification of a six-gene signature predicting overall survival for hepatocellular carcinoma. Cancer Cell Int. 2019; 19:138. PMC: 6528264. DOI: 10.1186/s12935-019-0858-2. View

19.

Haqq C, Nosrati M, Sudilovsky D, Crothers J, Khodabakhsh D, Pulliam B . The gene expression signatures of melanoma progression. Proc Natl Acad Sci U S A. 2005; 102(17):6092-7. PMC: 1087936. DOI: 10.1073/pnas.0501564102. View

20.

Serao N, Delfino K, Southey B, Beever J, Rodriguez-Zas S . Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival. BMC Med Genomics. 2011; 4:49. PMC: 3127972. DOI: 10.1186/1755-8794-4-49. View