| In recent years,the incidence of prostate cancer(PCa)in China has increased significantly.Ionizing radiation therapy(radiotherapy)is a common and well-established treatment for prostate cancer.Ferroptosis,a novel form of regulated cell death distinguished from apoptosis,necrosis,and autophagy in 2012,is ferroptosis dependent.Radiotherapy utilizes high-energy ionizing radiation(IR)to cause DNA double strands to break,inducing various cell death including cell cycle arrest,senescence.However,whether IR can induce cell death independent of DNA damage(such as ferroptosis)is currently unknown,and the role of ferroptosis in the ionizing radiation response remains poorly understood.This study is the first to use a Bibliometric Approach to build a library of articles indexed by web of science with the keywords " ferroptosis " and " cancer " over nearly a decade.The hot spots and research directions of ferroptosis in cancer are analyzed.Cluster analysis of information from authors,keywords,citations of included articles identified the following hot areas in the field of ferroptosis cancer:cancer therapy,survival,lipid peroxidation,reactive oxygen radicals,etc.Of these,the focus has been on the direction of cancer therapy,so we used m RNA sequencing and clinical information of prostate cancer patients from the Cancer Genome Atlas(TCGA)database,and differential analysis based on the ferroptosis database,Ferr Db V2,yielded seven prognostic genes associated with ferroptosis,AKR1C2,CDCA3,EZH2,MIOX,NOX1,PVT1,RRM2.The genes identified as risk markers were subjected to lasso regression analysis to build a model,and model validation was performed based on the high-throughput gene expression omnibus data base(GEO)gse70770 dataset.According to the ROC curve and K-M analysis results,the 7-gene model exhibited good survival prognosis prediction ability.Secondly to verify whether IR could induce prostate cancer cells to undergo ferroptosis,we performed IR on prostate cancer cell lines DU145 and PC-3 and detected ferroptosis related indicators.Cells exposed to IR showed significant changes in cell morphology,clonogenicity,proliferative capacity and intracellular levels of ROS,MDA and Fe2+.The results of Western blot assay and real-time PCR showed the same significant changes in the expression of ferroptosis related proteins;Administration of a ferroptosis agonist versus an inhibitor to IR prostate cancer cells produced marked changes in indices associated with intracellular ferroptosis.It was thus shown that IR can induce ferroptosis in prostate cancer cells.Finally,we performed sequencing analysis of the transcriptome of prostate cancer cells after IR,which yielded differentially expressed genes in the transcriptome of radiation sensitive prostate cancer cells,intersected the differentially expressed prognostic genes in ferroptosis related prostate cancer obtained from the isogenic signal analysis,and obtained an i IR sensitive differentially expressed gene in prostate cancer associated with ferroptosis,AKR1C2.The q R-PCR was further used to verify its expression,and it was found that the gene was highly expressed in cells after IR;Moreover,the expression of this gene in cells after IR was significantly upregulated by ferroptosis agonists,and the upregulation varied significantly with time.In summary,this study identified AKR1C2 as a radiation sensitive ferroptosis associated prostate cancer differential prognostic gene through bibliometric and bioinformatics approaches,and explored its role in prostate cancer development and the ferroptosis pathway and preliminarily identified the involvement of AKR1C2 in radiation response;This study provides some basic data for IR in the clinical treatment of prostate cancer and related research on the ferroptosis pathway,and AKR1C2,as an anti-tumor and radiation sensitizing gene in prostate cancer,is expected to be used to develop new treatments for prostate cancer based on ferroptosis and provide a new line of thinking in the treatment of prostate cancer. |
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