Uncovering immune cell-associated genes in breast cancer : based on summary data-based Mendelian randomized analysis and colocalization study
Liu, Jingyang ; Sun, Wen ; Li, Ning ; Li, Haibin ; Wu, Lijuan ; Yi, Huan LU ; Ji, Jianguang LU
and Zheng, Deqiang
LU
(2024)
In Breast cancer research : BCR
26.
- Abstract
BACKGROUND: Breast cancer, which is the most prevalent form of cancer among women globally, encompasses various subtypes that demand distinct treatment approaches. The tumor microenvironment and immune response are of crucial significance in the development and progression of breast cancer. Nevertheless, there has been scant evidence concerning the genes within breast cancer - specific immune cells.
METHODS: We utilized summary data-based Mendelian randomization (SMR) to identify genes associated with breast cancer by utilizing expression quantitative trait loci (eQTL) datasets for 14 different immune cell types and genome-wide association studies (GWAS) for overall breast cancer and its subtypes. Furthermore, colocalization... (More)
BACKGROUND: Breast cancer, which is the most prevalent form of cancer among women globally, encompasses various subtypes that demand distinct treatment approaches. The tumor microenvironment and immune response are of crucial significance in the development and progression of breast cancer. Nevertheless, there has been scant evidence concerning the genes within breast cancer - specific immune cells.
METHODS: We utilized summary data-based Mendelian randomization (SMR) to identify genes associated with breast cancer by utilizing expression quantitative trait loci (eQTL) datasets for 14 different immune cell types and genome-wide association studies (GWAS) for overall breast cancer and its subtypes. Furthermore, colocalization analysis was carried out to evaluate whether the observed association in SMR analyses is influenced by the same causal variant. Replication analysis and bulk RNA sequencing (bulkRNA-seq) analysis were employed to validate promising immune genes as potential drug targets.
RESULTS: After correcting for the rate of false discovery, we discovered a total of 17 genes in 9 immune cell types that were significantly associated with overall breast cancer and its subtypes. The genes KCNN4, L3MBTL3, ZBTB38, MDM4, and TNFSF10 were identified in overall breast cancer and its subtypes. Colocalization analyses provided robust evidence in support of these associations. Notably, the KCNN4 gene in non-classical MONOcytes (MONOnc) was further validated through replication analysis and bulkRNA-seq analysis.
CONCLUSION: In summary, our research has revealed a repertoire of genes within diverse immune cells associated with breast cancer. KCNN4 gene in non-classical MONOcytes (MONOnc) exhibited a negative association with overall breast cancer and its subtypes, which was identified as a potential drug target for breast cancer, opening up new avenues for therapeutic interventions.
(Less)
- author
- Liu, Jingyang
; Sun, Wen
; Li, Ning
; Li, Haibin
; Wu, Lijuan
; Yi, Huan
LU
; Ji, Jianguang
LU
and Zheng, Deqiang
LU
- publishing date
- 2024-11-29
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Humans, Breast Neoplasms/genetics, Female, Quantitative Trait Loci, Genome-Wide Association Study, Mendelian Randomization Analysis, Genetic Predisposition to Disease, Biomarkers, Tumor/genetics, Polymorphism, Single Nucleotide, Tumor Microenvironment/immunology, Gene Expression Regulation, Neoplastic
- in
- Breast cancer research : BCR
- volume
- 26
- article number
- 172
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85211181351
- pmid:39614330
- ISSN
- 1465-5411
- DOI
- 10.1186/s13058-024-01928-0
- language
- English
- LU publication?
- no
- additional info
- © 2024. The Author(s).
- id
- c42c8e24-56db-4226-962b-6bec365e1960
- date added to LUP
- 2024-12-01 14:12:37
- date last changed
- 2025-07-05 16:40:20
@article{c42c8e24-56db-4226-962b-6bec365e1960,
abstract = {{<p>BACKGROUND: Breast cancer, which is the most prevalent form of cancer among women globally, encompasses various subtypes that demand distinct treatment approaches. The tumor microenvironment and immune response are of crucial significance in the development and progression of breast cancer. Nevertheless, there has been scant evidence concerning the genes within breast cancer - specific immune cells.</p><p>METHODS: We utilized summary data-based Mendelian randomization (SMR) to identify genes associated with breast cancer by utilizing expression quantitative trait loci (eQTL) datasets for 14 different immune cell types and genome-wide association studies (GWAS) for overall breast cancer and its subtypes. Furthermore, colocalization analysis was carried out to evaluate whether the observed association in SMR analyses is influenced by the same causal variant. Replication analysis and bulk RNA sequencing (bulkRNA-seq) analysis were employed to validate promising immune genes as potential drug targets.</p><p>RESULTS: After correcting for the rate of false discovery, we discovered a total of 17 genes in 9 immune cell types that were significantly associated with overall breast cancer and its subtypes. The genes KCNN4, L3MBTL3, ZBTB38, MDM4, and TNFSF10 were identified in overall breast cancer and its subtypes. Colocalization analyses provided robust evidence in support of these associations. Notably, the KCNN4 gene in non-classical MONOcytes (MONOnc) was further validated through replication analysis and bulkRNA-seq analysis.</p><p>CONCLUSION: In summary, our research has revealed a repertoire of genes within diverse immune cells associated with breast cancer. KCNN4 gene in non-classical MONOcytes (MONOnc) exhibited a negative association with overall breast cancer and its subtypes, which was identified as a potential drug target for breast cancer, opening up new avenues for therapeutic interventions.</p>}},
author = {{Liu, Jingyang and Sun, Wen and Li, Ning and Li, Haibin and Wu, Lijuan and Yi, Huan and Ji, Jianguang and Zheng, Deqiang}},
issn = {{1465-5411}},
keywords = {{Humans; Breast Neoplasms/genetics; Female; Quantitative Trait Loci; Genome-Wide Association Study; Mendelian Randomization Analysis; Genetic Predisposition to Disease; Biomarkers, Tumor/genetics; Polymorphism, Single Nucleotide; Tumor Microenvironment/immunology; Gene Expression Regulation, Neoplastic}},
language = {{eng}},
month = {{11}},
publisher = {{BioMed Central (BMC)}},
series = {{Breast cancer research : BCR}},
title = {{Uncovering immune cell-associated genes in breast cancer : based on summary data-based Mendelian randomized analysis and colocalization study}},
url = {{http://dx.doi.org/10.1186/s13058-024-01928-0}},
doi = {{10.1186/s13058-024-01928-0}},
volume = {{26}},
year = {{2024}},
}