Qi Ying, Zhao Pengfei
Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, China.
Front Oncol. 2024 Aug 29;14:1436874. doi: 10.3389/fonc.2024.1436874. eCollection 2024.
Breast cancer, as the most prevalent malignancy among women globally, continues to exhibit rising incidence rates, particularly in China. The disease predominantly affects women aged 40 to 60 and is influenced by both genetic and environmental factors. This study focuses on the role of H19 gene polymorphisms, investigating their impact on breast cancer susceptibility, clinical outcomes, and response to treatment.
We engaged 581 breast cancer patients and 558 healthy controls, using TaqMan assays and DNA sequencing to determine genotypes at specific loci (rs11042167, rs2071095, rs2251375). We employed hybridization and immunohistochemistry to measure the expression levels of LincRNA H19, miR-675, MRP3, HOXA1, and MMP16 in formalin-fixed, paraffin-embedded samples. Statistical analyses included chi-squared tests, logistic regression, and Kaplan-Meier survival curves to evaluate associations between genetic variations, gene expression, and clinical outcomes.
Genotypes AG at rs11042167, GT at rs2071095, and AC at rs2251375 were significantly associated with increased risk of breast cancer. Notably, the AA genotype at rs11042167 and TT genotype at rs2071095 were linked to favorable prognosis. High expression levels of LincRNA H19, miR-675, MRP3, HOXA1, and MMP16 in cancer tissues correlated with advanced disease stages and poorer survival rates. Spearman correlation analysis revealed significant positive correlations between the expression of LincRNA H19 and miR-675 and specific genotypes, highlighting their potential regulatory roles in tumor progression.
The study underscores the critical roles of LincRNA H19 and miR-675 as prognostic biomarkers in breast cancer, with their overexpression associated with disease progression and adverse outcomes. The H19/LincRNA H19/miR-675/MRP3-HOXA1-MMP16 axis offers promising targets for new therapeutic strategies, reflecting the complex interplay between genetic markers and breast cancer pathology.
The findings confirm that certain H19 SNPs are associated with heightened breast cancer risk and that the expression profiles of related genetic markers can significantly influence prognosis and treatment response. These biomarkers hold potential as targets for personalized therapy and early detection strategies in breast cancer, underscoring the importance of genetic research in understanding and managing this disease.
乳腺癌是全球女性中最常见的恶性肿瘤，其发病率持续上升，在中国尤其如此。该疾病主要影响40至60岁的女性，受遗传和环境因素的影响。本研究聚焦于H19基因多态性的作用，探究其对乳腺癌易感性、临床结局及治疗反应的影响。
我们招募了581例乳腺癌患者和558例健康对照，采用TaqMan分析和DNA测序来确定特定位点（rs11042167、rs2071095、rs2251375）的基因型。我们运用杂交和免疫组化方法来测量福尔马林固定、石蜡包埋样本中LincRNA H19、miR - 675、MRP3、HOXA1和MMP16的表达水平。统计分析包括卡方检验、逻辑回归和Kaplan - Meier生存曲线，以评估基因变异、基因表达与临床结局之间的关联。
rs11042167位点的AG基因型、rs2071095位点的GT基因型和rs2251375位点的AC基因型与乳腺癌风险增加显著相关。值得注意的是，rs11042167位点的AA基因型和rs2071095位点的TT基因型与良好预后相关。癌组织中LincRNA H19、miR - 675、MRP3、HOXA1和MMP16的高表达水平与疾病晚期和较差的生存率相关。Spearman相关性分析显示LincRNA H19和miR - 675的表达与特定基因型之间存在显著正相关，突出了它们在肿瘤进展中的潜在调控作用。
该研究强调了LincRNA H19和miR - 675作为乳腺癌预后生物标志物的关键作用，它们的过表达与疾病进展和不良结局相关。H19/LincRNA H19/miR - 675/MRP3 - HOXA1 - MMP16轴为新的治疗策略提供了有前景的靶点，反映了遗传标志物与乳腺癌病理学之间的复杂相互作用。
研究结果证实某些H19单核苷酸多态性与乳腺癌风险增加相关，且相关遗传标志物的表达谱可显著影响预后和治疗反应。这些生物标志物有望成为乳腺癌个性化治疗和早期检测策略的靶点，强调了基因研究在理解和管理该疾病中的重要性。
