Ferroptosis typing of osteosarcoma and the screening and verification of its markers

Abstract

Abstract Osteosarcoma (OS) is an aggressive cancer characterized by a poor prognosis.It primarily affects young individuals and has a survival rate of less than five years.Lately, there has been an increasing fascination with the involvement of ferroptosis, a cell death pathway that relies on iron, in cancer stem cells(CSCs) and its potential as a focus for enhancing the effectiveness of cancer treatment.Nonetheless, the role of the iron death pathway in OS is still unclear. In our investigation, we employed WGCNA and PPI network analysis to discover pivotal hub genes (YRDC,ARPC5,EIF2S1, CAPZA1).Subsequently, we examined the correlation between the expression of these genes in protein samples from tissue chips and the clinical information of osteosarcoma using immunohistochemistry.In addition, we confirmed the levels of YRDC, ARPC5, EIF2S1, and CAPZA1 expression in OS and healthy osteoblasts through rt-PCR and Western Blot methods.In order to assess the influence of these four genes on the growth and ability to form colonies of cells, we performed MTT and clonogenic tests. Our findings strongly indicate a notable correlation between the levels of protein expression of YRDC, ARPC5, EIF2S1, and CAPZA1 and the Enneking stage of OS, along with the occurrence of lymph node metastasis.Furthermore, these proteins showed a direct association with the growth and ability of OS cells to form colonies.To summarize, the genes YRDC, ARPC5, EIF2S1, and CAPZA1 show potential as diagnostic indicators and targets for treatment in the iron death pathway of osteosarcoma.