MCM6是乳腺癌中的一种预后不良生物标志物,促进了其进展。
MCM6 is a Poor Prognostic Biomarker and Promotes Progression in Breast Cancer.
发表日期:2023 Aug 30
作者:
Zi Lei, Peng Wang, Da-Qi Jia, Lei-Lei Li, Yi-Peng Wu, Yuan Yang, Guo-Qing Pan
来源:
Cell Death & Disease
摘要:
乳腺癌是全球最常见的恶性肿瘤,也是癌症导致死亡的主要原因。MCM6对于癌症发生至关重要,但MCM6的病因仍不清楚。通过癌症基因组图谱数据库(TCGA)、免疫组织化学、定量实时荧光PCR(qRT-PCR)和免疫印迹等方法,研究了乳腺癌患者中MCM6的表达情况。采用Kaplan-Meier法和Cox回归分析评估了预后因素。基于多变量Cox回归分析选择的关键因素,采用Nomogram风险预测模型进行临床风险评估。利用TCGA数据库确定MCM6与化疗敏感性、免疫检查点相关基因(ICGs)、肿瘤浸润免疫细胞以及肿瘤突变负荷(TMB)和甲基化之间的相关性。通过CCK实验、流式细胞术、划痕愈合实验、Transwell实验和异种移植实验研究了MCM6对肿瘤细胞的增殖、细胞周期以及迁移和侵袭行为的影响。乳腺癌患者中MCM6的表达上调,与肿瘤大小(p = 0.001)和淋巴结转移(p = 0.012)密切相关。多元分析表明MCM6是乳腺癌预后的独立危险因素。Nomogram预测模型包括MCM6、年龄、ER、M和N分期,具有良好的判别能力,C指数为0.817,校准良好。MCM6的过表达与化疗敏感性、免疫检查点相关基因(ICGs)、肿瘤浸润免疫细胞、肿瘤突变负荷(TMB)和甲基化相关。沉默MCM6能显著抑制增殖,延长细胞周期中的G1期,并抑制癌细胞的增殖、迁移和侵袭行为,同时在体内抑制肿瘤生长。我们的研究表明,MCM6在乳腺癌中高度表达,并可作为独立的预后因子,有望成为乳腺癌治疗的新靶点。© 2023 The Author(s). Published by IMR Press.
Breast cancer is the commonest global malignancy and the primary cause of carcinoma death. MCM6 is vital to carcinogenesis, but the pathogenesis of MCM6 remains unclear.MCM6 expression in patients with breast cancer was examined through The Cancer Genome Atlas (TCGA) database, immunohistochemistry, Quantitative Real-Time PCR (qRT‒PCR) and Western blotting. The prognostic factors were assessed by the Kaplan‒Meier method and Cox regression. On the basis of the key factors selected by multivariable Cox regression analysis, a nomogram risk prediction model was adopted for clinical risk assessment. The TCGA database was utilized to determine how MCM6 is correlated with chemotherapy sensitivity, immune checkpoint-related genes (ICGs), tumor-infiltrating immune cells, along with tumor mutation burden (TMB) and methylation. The impact of MCM6 on carcinoma cells was investigated in terms of proliferation, cell cycle as well as migrating and invasive behavior through CCK assays, flow cytometry, wound healing assays, Transwell assays and xenotransplantation experiments.MCM6 expression was upregulated, which is closely associated with the size of the tumor (p = 0.001) and lymph node metastasis (p = 0.012) in patients with breast cancer. Multivariate analysis revealed MCM6 to be an independent risk factor for prognosis in patients with breast carcinoma. The nomograph prediction model included MCM6, age, ER, M and N stage, which displayed good discrimination with a C index of 0.817 and good calibration. Overexpression of MCM6 correlated with chemotherapy sensitivity, immune checkpoint-related genes (ICGs), tumor-infiltrating immune cells, tumor mutation burden (TMB), and methylation. Silencing MCM6 significantly inhibited proliferation, prolonged the G1 phase of the cell cycle, and restrained the proliferation, migration and invasive behavior of cancerous cells and inhibited tumor growth in vivo.Our research shows that MCM6 is highly expressed in breast cancer and can be used as an independent prognostic factor, which is expected to become a new target for the treatment of breast cancer in the future.© 2023 The Author(s). Published by IMR Press.