Relationship between ferroptosis-related genes expression and prognosis of colorectal cancer patients
Objective To investigate the differential expressions of ferroptosis-related genes in colorectal cancer(CRC)patients and analyze the relationship between gene expressions and patients prognosis.Methods GSE32323,GSE21510 and GSE934 of CRC gene expression profile data from Gene Expression Omnibus(GEO)database and ferroptosis-related gene data sets were selected to screen differentially expressed ferroptosis-related genes in CRC patients.Protein-protein interaction(PPI)network construction,gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)signaling pathway enrichment were performed for the selected co-differentially expressed genes,and the correlation between immune cell infiltration and gene expression level was estimated.Meanwhile,the CRC patients were divided into the high and low expression groups according to the expression level of co-differentially expressed genes,and the overall survival(OS)and progression-free survival(PFS)of two groups were compared.Paraffin sections of 44 CRC tissues surgically removed in Lishui People's Hospital from January 2018 to December 2023 were retrospectively analyzed.Immunohistoche-mistry was used to detect the expression levels of co-differentially expressed gene proteins in cancer tissues of the patients,and their relationship with clinicopathological features was analyzed.Results There were three co-differentially expressed genes,named MYC,voltage dependent anion channel protein 3(VDAC3)gene and hypoxia inducible lipid droplet associated gene(HILPDA)in the four data sets,and 33 nodes and 219 interactions between nodes were found by the PPI analysis,with the average clustering index of 0.68.Enrichment analysis showed that the functions of the three genes were mainly concentrated in transcriptional regulation,DNA template,karyoplasm and transcription factor binding,while the signaling pathways were mainly enriched in cancer,cell cycle and ferroptosis.The PFS and OS of CRC patients with high VDAC3 gene expression were significantly lower than those of the low expression group(both P＜0.05),while there was no significant difference in OS and PFS of CRC patients with high vs.low MYC and HILPDA expressions(all P＞0.05).In colon cancer,the expression level of VDAC3 was correlated with B lymphocyte,CD8+T lymphocyte,CD4+T lymphocyte and neutrophil infiltration(all P＜0.05),and in rectal cancer,VDAC3 expression level was correlated with CD8+T lymphocyte and CD4+T lymphocyte infiltration(both P＜0.05).Immunohistochemistry showed that VDAC3 was positively expressed in cytoplasm.VDAC3 was positively expressed in 20(45.5％)of the 44 CRC tissues,and showed differences in tumor differentiation and vascular invasion between VDAC3 positive expression group and negative expression group(both P＜0.05).Conclusion MYC,VDAC3 gene and HILPDA are differentially expressed genes associated with ferroptosis in CRC.Low expression of VDAC3 gene is associated with poor prognosis of CRC patients.
万方数据
维普
