This study was performed to investigate the prognostic value of JCHAIN gene in the distant metastasis(DM)of breast cancer(BC)and its possible regulatory mechanism through bioinformatics analysis.TCGA database BC transcriptome sequencing data were grouped according to sample source,and LIMMA was used to identify differentially expressed genes(DEGs),and combined with clinical data,genes related to tumorigenesis and metastasis were further screened.Single-factor Cox analysis revealed that 10 key genes were significantly associated with OS,while multi-factor Cox analysis further filtered out 4 genes with significant correlation.The analysis algorithm of 8 immune infiltration cell subtypes were used to evaluate the correlation of JCHAIN expression level with the subtype of infiltrating cells and the proportion of each cellular component in the tumor microenvironment.the genome-wide drug sensitivity of anti-cancer drugs(GDSC)database was used to analyze the chemotherapy drug sensitivity of BC patients with different JCHAIN expression levels;dual-luciferase reporter system was used to explore the mechanism of low JCHAIN expression in BC with DM.Based on the screened key genes,a prognostic model was successfully constructed,and it was found that with the increase of model risk value,the gene expression of JCHAIN and TUBA3D showed a down-regulation trend,while the gene expression of SPDYC and CRISP3 was up-regulated.②The expression of gene JCHAIN in BC patients with DM was lower than those in patients without DM and normal controls.In clinical outcomes,the expression level of gene JCHAIN in the death group was lower than that in the survival group,and with the progression of the disease(stage)or the deepening of malignancy,the expression of gene JCHAIN basically showed a downward trend.The number of immune cells in the JCHAIN high expression group was generally higher than that in the low expression group.For example,among the six algorithms that predict the expression of B cells and T cells(CD4+/CD8+),the JCHAIN high expression group is higher than the low expression group.Based on the GDSC database,the JCHAIN expression level could predict the chemotherapeutic drug sensitivity,and the expression level is positively correlated with the drug sensitivity.The luciferase detection value of the experimental group with the participation of the recombinant plasmid of transcription factor TWIST1(TW)was lower than that of the control group without the participation of the TW recombinant plasmid.Taken together,JCHAIN and TUBA3D are protective factor against risk for BC,while SPDYC and CRISP3 are risk factor;lower JCHAIN level may promote the occurrence and DM of BC,while higher JCHAIN level may promote the infiltration of various immune cells.Furthermore,BC patients with high expression of JCHAIN may have higher sensitivity to therapeutic drugs than those with low expression.The transcription factor TW can bind to the JCHAIN promoter sequence and perform negative regulation.
关键词
乳腺癌/JCHAIN/远处转移/预后价值/生物信息学
Key words
Breast cancer/JCHAIN/Distance metastasis/Prognostic value/Bioinformatics
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