Identification of Novel Diagnostic Biomarkers in Triple-Negative Breast Cancer Through Analysis of Polymorphic SNPs and APA Events SNP and APA Biomarkers in Triple-Negative Breast Cancer

Daiyun Dong (1), Yuzhang Tao (2), Xiaoming Wu (3)
(1) Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, United States,
(2) Bachelor of Medicine, bZonglian College, Xi'an Jiaotong University, Xi'an, Shaanxi, China, China,
(3) The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, China, China

Abstract

Background: As a subtype of breast cancer, triple-negative breast cancer (TNBC) exhibits unique pathological phenotypes and severe morbidity trends. New evidence suggests that aberrant alternative polyadenylation (APA) events can be regulated by single nucleotide polymorphisms (SNPs) and are associated with breast cancer. The study aimed to identify the APA-associated susceptibility SNP in TNBC, which may be useful in screening and treatment.


Methods: The RNA sequencing data is from 285 tumor tissues and 66 normal tissues of TNBC patients, accessed from the NCBI dataset FUSCCTNBC (Accession: PRJNA486023). We analyzed gene expression levels, APA events, and APA-associated SNPs, and explored their relationships and influences on TNBC.


Results: Our study revealed significant differences in both gene expression and APA events between tumor and normal tissues of TNBC patients. The differentially expressed genes are enriched in protein transcription, folding, localization, and targeting. apaQTL analysis indicated significant associations between APA events of genes and SNPs. We found that the APA event of the transmembrane p24 trafficking protein 9 (TMED9) is highly related to the SNP rs3749822, where the G allele would decrease the Poly-A length of TMED9 and increase its expression level.


Conclusion: The study elucidates the significant association between SNP rs3749822 and the APA event of the TMED9 gene, as well as their influences on TNBC, highlighting the susceptibility of SNP rs3749822 allele G for TNBC. Our findings provide new directions for further exploration of SNPs affecting APA events, aiding in identifying disease-susceptible populations.

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Authors

Daiyun Dong
Yuzhang Tao
Xiaoming Wu
wxm@mail.xjtu.edu.cn (Primary Contact)
1.
Dong D, Tao Y, Wu X. Identification of Novel Diagnostic Biomarkers in Triple-Negative Breast Cancer Through Analysis of Polymorphic SNPs and APA Events: SNP and APA Biomarkers in Triple-Negative Breast Cancer. Arch Breast Cancer [Internet]. [cited 2024 Dec. 11];12(1). Available from: https://archbreastcancer.com/index.php/abc/article/view/1015

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