MZB1的可变剪接事件是乳腺癌内分泌治疗耐药的潜在生物标志物

doi:10.11904/j.issn.1002-3070.2024.05.006

Abstract

Abstract: Objective The aim of this study was to use bioinformatics methods to integrate gene expression profiles and splicing profiles,and identify potential biomarkers that play a role in endocrine therapy resistance. Methods The gene datasets of endocrine therapy sensitive and resistant cells from the Gene expression omnibus(GEO)database were downloaded to screen for differentially expressed genes and differential splicing genes related to endocrine therapy resistance,and perform Hallmark enrichment analysis and Gene set enrichment analysis(GSEA)on these genes.The cancer genome atlas(TCGA)and the breast cancer data in the Molecular taxonomy of breast cancer international consortium(METABRIC)were downloaded,and compared the expression of differential genes in tumor and adjacent tissues,as well as the differences between different tumor stages and grades.The relationship between differential expressed genes and overall survival(OS),alternative splicing,and immune infiltration were explored in patients receiving endocrine therapy. Results GEO data analysis showed that differentially expressed genes were mainly enriched in breast cancer treatment response related to pathways and immune-related pathways,and differentially spliced genes were mainly enriched in breast cancer treatment response related to pathways.The genes that undergo differential expression and splicing simultaneously included CAMK2B,EVL,MZB1and PTPRG.Among them,the expression of MZB1 was associated with OS and immune cell infiltration in patients receiving endocrine therapy,and the precursor mRNA of MZB1 underwent more alternative 3′splicing in drug-resistant cells. Conclusion The expression of MZB1 is related to the effect on endocrine therapy in breast cancer,and its mechanism may be the change of immune related function caused by alternative splicing.MZB1 can serve as a potential biomarker for endocrine therapy to improve prognosis.

Key words: Breast cancer, Endocrine therapy, Alternative splicing, Immune infiltration

CLC Number:

R737.9

ZHANG Yuqing, JING Jing, LIU Zhaoliang, AN Jing, AN Weiwei. The alternative splicing event of MZB1 is a potential biomarker of drug resistance in endocrine therapy of breast cancer[J]. Journal of Practical Oncology, 2024, 38(5): 313-322.

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URL: http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/10.11904/j.issn.1002-3070.2024.05.006

http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/Y2024/V38/I5/313

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The alternative splicing event of MZB1 is a potential biomarker of drug resistance in endocrine therapy of breast cancer

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