The alternative splicing event of MZB1 is a potential biomarker of drug resistance in endocrine therapy of breast cancer
10.11904/j.issn.1002-3070.2024.05.006
- VernacularTitle: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
- Author:
Yuqing ZHANG
1
;
Jing JING
;
Zhaoliang LIU
;
Jing AN
;
Weiwei AN
Author Information
1. 哈尔滨医科大学肿瘤防治研究所(哈尔滨 150081)
- Publication Type:Journal Article
- Keywords:
Breast cancer;
Endocrine therapy;
Alternative splicing;
Immune infiltration
- From:
Practical Oncology Journal
2024;38(5):313-322
- CountryChina
- Language:Chinese
-
Abstract:
Objective The aim of this study was to use bioinformatics methods to integrate gene expression profiles and spli-cing profiles,and identify potential biomarkers that play a role in endocrine therapy resistance.Methods The gene datasets of endo-crine therapy sensitive and resistant cells from the Gene expression omnibus(GEO)database were downloaded to screen for differenti-ally 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 Molecu-lar 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 dif-ferential 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 treat-ment response related to pathways and immune-related pathways,and differentially spliced genes were mainly enriched in breast canc-er 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 pa-tients 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.
