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. 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. 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+ receptor staining. Ingenuity Pathway Analysis (IPA) showed key genes highly enriched in BC with CDKN2B-AS1. 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.

中文翻译：

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细胞周期蛋白依赖性激酶抑制剂 2B 反义 RNA 1 基因表达和 rs2383207 变异与乳腺癌风险和生存的关联

失调的长链非编码 RNA (lncRNA) 和相关遗传变异的表达特征涉及肿瘤发生、进展和复发的每个阶段。本研究旨在探讨 lncRNA 细胞周期蛋白依赖性激酶抑制剂 2B 反义 RNA 1 (CDKN2B-AS1) 基因表达和 rs2383207A>G 内含子变异与乳腺癌 (BC) 风险和预后的关联，并验证其分子作用和网络这种lncRNA在BC中通过生物信息学基因分析。血清 CDKN2B-AS1 相对表达和 rs2383207 基因型在 214 名无关女性（104 名原发性 BC 和 110 名对照）中使用实时 PCR 确定。还检索了来自癌症基因组图谱 (TCGA) 的 16 项 BC 研究，包括 8925 名患者，以验证结果。与对照组相比，BC 患者的 CDKN2B-AS1 血清水平上调。在纯合子 (OR = 3.27, 95% CI 1.20–8.88, P = 0.044) 和隐性 (OR = 3.17, 95% CI 1.20–8.34, P = 0.013) 模型下，A/A 基因型携带者患 BC 的可能性高出三倍. G/G 纯合子患者的表达水平 [中位数和四分位数为 3.14 (1.52–4.25)] 高于 A/G [1.42 (0.93–2.35)] 和 A/A [1.62 (1.33–2.51)] 队列 (P = 0.006）。Kaplan-Meier 曲线还显示 G/G 队列的平均生存期（20.6 个月）高于对应队列（A/A：15.8 和 A/G：17.2 个月）（P < 0.001）。一致地，BC 数据集显示在高表达水平的队列中存活率更高（P = 0.003）。主成分分析 (PCA) 显示生存期较短的患者偏向于 A/A 和 A/G 基因型、多发病变、晚期、淋巴血管浸润和 HER2+ 受体染色。Ingenuity Pathway Analysis (IPA) 显示关键基因在 BC 中高度富集 CDKN2B-AS1。这些发现支持 CDKN2B-AS1 作为 BC 表观遗传标记的推定作用，并为其作为此类癌症的治疗分子靶标的潜在用途开辟了新途径。