The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 110301, Taiwan.
EG BioMed US Inc., Covina, CA 91722, USA.
Biomolecules. 2024 May 12;14(5):571. doi: 10.3390/biom14050571.
Breast cancer is a leading cause of cancer mortality in women worldwide. Using the Infinium MethylationEPIC BeadChip, we analyzed plasma sample methylation to identify the gene in breast cancer patients. We assessed -related roles and pathways for their biomarker potential. To verify the methylation status, quantitative methylation-specific PCR (qMSP) was performed on genomic DNA and circulating cell-free DNA samples, and mRNA expression analysis was performed using RT‒qPCR. The results were validated in a Western population; for this analysis, the samples included plasma samples from breast cancer patients from the USA and from The Cancer Genome Atlas (TCGA) cohort. To study the pathway, we conducted cell viability assays, gene manipulation and RNA sequencing. hypermethylation was identified in 61.8% of breast cancer tissues from Taiwanese patients, exhibiting specificity to this malignancy. Furthermore, its presence correlated significantly with unfavorable 5-year overall survival outcomes. The levels of methylated in the blood of patients from Taiwan and the USA correlated with the stage of breast cancer. The proportion of patients with high methylation levels increased from 0% in healthy individuals to 63.6% in Stage 0, 80% in Stage I and 82.6% in Stage II, with a sensitivity of 78.5%, an accuracy of 90.3% and a specificity of 100%. hypermethylation was significantly correlated with increased mRNA expression ( < 0.001). Knockdown of SRCIN1 decreased the viability of breast cancer cells. silencing resulted in the downregulation of ESR1, BCL2 and various cyclin protein expressions. hypermethylation in the blood may serve as a noninvasive biomarker, facilitating early detection and prognosis evaluation, and -targeted therapies could be used in combination regimens for breast cancer patients.
乳腺癌是全球女性癌症死亡的主要原因。我们使用 Infinium MethylationEPIC BeadChip 分析血浆样本的甲基化,以鉴定乳腺癌患者中的基因。我们评估了与相关的作用和途径,以评估其作为生物标志物的潜力。为了验证甲基化状态,我们对基因组 DNA 和循环无细胞 DNA 样本进行了定量甲基化特异性 PCR (qMSP),并使用 RT-qPCR 进行了 mRNA 表达分析。在西方人群中进行了验证分析;在此分析中,样本包括来自美国和癌症基因组图谱 (TCGA) 队列的乳腺癌患者的血浆样本。为了研究途径,我们进行了细胞活力测定、基因操作和 RNA 测序。我们在来自台湾患者的乳腺癌组织中发现了 基因的高度甲基化,这种甲基化特异性与这种恶性肿瘤有关。此外,其存在与不利的 5 年总生存结果显著相关。来自台湾和美国的患者血液中甲基化的水平与乳腺癌的分期相关。高甲基化水平患者的比例从健康个体中的 0%增加到 0 期的 63.6%、I 期的 80%和 II 期的 82.6%,灵敏度为 78.5%,准确性为 90.3%,特异性为 100%。基因的高甲基化与 mRNA 表达的增加显著相关(<0.001)。SRCIN1 的敲低降低了乳腺癌细胞的活力。基因沉默导致 ESR1、BCL2 和各种细胞周期蛋白表达的下调。血液中的基因甲基化可能作为一种非侵入性的生物标志物,有助于早期检测和预后评估,并且针对的治疗方法可以与乳腺癌患者的联合治疗方案一起使用。