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Association of cyclin-dependent kinase inhibitor 2B antisense RNA 1 gene expression and rs2383207 variant with breast cancer risk and survival.
- Source :
-
Cellular & molecular biology letters [Cell Mol Biol Lett] 2021 Apr 13; Vol. 26 (1), pp. 14. Date of Electronic Publication: 2021 Apr 13. - Publication Year :
- 2021
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Abstract
- Background: The expression signature of deregulated long non-coding RNAs (lncRNAs) and related genetic variants is implicated in every stage of tumorigenesis, progression, and recurrence. This study aimed to explore the association of lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene expression and the rs2383207A>G intronic variant with breast cancer (BC) risk and prognosis and to verify the molecular role and networks of this lncRNA in BC by bioinformatics gene analysis.<br />Methods: Serum CDKN2B-AS1 relative expression and rs2383207 genotypes were determined in 214 unrelated women (104 primary BC and 110 controls) using real-time PCR. Sixteen BC studies from The Cancer Genome Atlas (TCGA) including 8925 patients were also retrieved for validation of results.<br />Results: CDKN2B-AS1 serum levels were upregulated in the BC patients relative to controls. A/A genotype carriers were three times more likely to develop BC under homozygous (OR = 3.27, 95% CI 1.20-8.88, P = 0.044) and recessive (OR = 3.17, 95% CI 1.20-8.34, P = 0.013) models. G/G homozygous patients had a higher expression level [median and quartile values were 3.14 (1.52-4.25)] than A/G [1.42 (0.93-2.35)] and A/A [1.62 (1.33-2.51)] cohorts (P = 0.006). The Kaplan-Meier curve also revealed a higher mean survival duration of G/G cohorts (20.6 months) compared to their counterparts (A/A: 15.8 and A/G: 17.2 months) (P < 0.001). Consistently, BC data sets revealed better survival in cohorts with high expression levels (P = 0.003). Principal component analysis (PCA) showed a deviation of patients who had shorter survival towards A/A and A/G genotypes, multiple lesions, advanced stage, lymphovascular invasion, and HER2 <superscript>+</superscript> receptor staining. Ingenuity Pathway Analysis (IPA) showed key genes highly enriched in BC with CDKN2B-AS1.<br />Conclusions: The findings support the putative role of CDKN2B-AS1 as an epigenetic marker in BC and open a new avenue for its potential use as a therapeutic molecular target in this type of cancer.
- Subjects :
- Adult
Alleles
Breast Neoplasms genetics
Breast Neoplasms mortality
Case-Control Studies
Discriminant Analysis
Female
Genotype
Homozygote
Humans
Kaplan-Meier Estimate
Middle Aged
Odds Ratio
Polymorphism, Single Nucleotide
Principal Component Analysis
Prognosis
RNA, Long Noncoding blood
RNA, Long Noncoding metabolism
Risk Factors
Up-Regulation
Breast Neoplasms pathology
RNA, Long Noncoding genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1689-1392
- Volume :
- 26
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cellular & molecular biology letters
- Publication Type :
- Academic Journal
- Accession number :
- 33849428
- Full Text :
- https://doi.org/10.1186/s11658-021-00258-9