Lai Gui-E, Zhou Jian, Huang Cui-Liu, Mai Cun-Jun, Lai Yi-Mei, Lin Zhi-Qin, Peng Tao, Luo Yuan, Liu Feng-En
Department of Vascular and Breast Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
Department of Neurosurgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Gland Surg. 2022 May;11(5):826-836. doi: 10.21037/gs-22-164.
DNA methylation status is strongly associated with the prognosis of breast invasive carcinoma (BRCA). Elucidating the mechanisms underlying DNA methylation coupled with determining its biological function is imperative to the effective development of treatment and prevention strategies for breast cancer.
We retrieved transcriptome and DNA methylation profiles of BRCA patients from The Cancer Genome Atlas (TCGA) database, then applied the "limma" package in R software to identify differentially expressed genes (DEGs) and aberrantly methylated genes. Next, we used the "MethylMix" package to screen for methylation-driven genes, and performed univariate and multivariate Cox regression analyses to determine the prognostic value of the methylation-driven genes and clinical characteristics. We validated these findings in 51 breast cancer tissues alongside 51 corresponding normal tissues. Furthermore, we used cell experiments to clarify the biological function and underlying molecular mechanisms of .
A total of 25 methylation-driven genes were identified in the dataset. Results from univariate and multivariate Cox regression showed that , , , and were significantly associated with patient prognosis. Immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) results showed that the expression levels of and were negatively correlated with BRCA stage, whereas those of and were positively correlated with BRCA stage. Results from experiments showed that knockdown expression promoted breast cancer cells proliferation, clone formation, and invasion. Up-regulation of inhibited breast cancer cells proliferation, clone formation, and invasion.
In summary, low expression is a significant prognostic factor for the survival of BRCA patients and thus could be a potential therapeutic target for the treatment of BRCA.
DNA甲基化状态与乳腺浸润性癌（BRCA）的预后密切相关。阐明DNA甲基化的潜在机制并确定其生物学功能对于有效制定乳腺癌的治疗和预防策略至关重要。
我们从癌症基因组图谱（TCGA）数据库中检索了BRCA患者的转录组和DNA甲基化谱，然后应用R软件中的“limma”包来识别差异表达基因（DEG）和异常甲基化基因。接下来，我们使用“MethylMix”包筛选甲基化驱动基因，并进行单变量和多变量Cox回归分析，以确定甲基化驱动基因和临床特征的预后价值。我们在51个乳腺癌组织和51个相应的正常组织中验证了这些发现。此外，我们使用细胞实验来阐明……的生物学功能和潜在分子机制。
数据集中共鉴定出25个甲基化驱动基因。单变量和多变量Cox回归结果显示，……与患者预后显著相关。免疫组织化学和定量实时聚合酶链反应（qRT-PCR）结果表明，……的表达水平与BRCA分期呈负相关，而……的表达水平与BRCA分期呈正相关。……实验结果表明，敲低……表达促进乳腺癌细胞增殖、克隆形成和侵袭。上调……抑制乳腺癌细胞增殖、克隆形成和侵袭。
总之，低……表达是BRCA患者生存的一个重要预后因素，因此可能是治疗BRCA的潜在治疗靶点。
