Jiang Huayong, Wang Bin, Zhang Fuli, Qian Yuanyu, Chuang Chia-Chen, Ying Mingzhen, Wang Yajie, Zuo Li
Department of Radiation Oncology, PLA Army General Hospital, Beijing 100700, China.
Department of Oncology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China.
Int J Mol Sci. 2016 Oct 28;17(11):1803. doi: 10.3390/ijms17111803.
Checkpoint kinase 2 (CHK2) and cell division cycle 25C (CDC25C) are two proteins involved in the DNA damage response pathway, playing essential roles in maintaining genome integrity. As one of the major hallmarks of abnormal cellular division, genomic instability occurs in most cancers. In this study, we identified the functional expression of pCHK2-Thr68 and pCDC25C-Ser216 in breast cancer, as well as its association with breast cancer survival. Tissue microarray analysis using immunohistochemistry was constructed to identify the expression of pCHK2-Thr68 and pCDC25C-Ser216 in 292 female breast cancer patients. The relationship among protein expression, clinicopathological factors (e.g., human epidermal growth factor receptor 2 (HER 2), tumor size, tumor-node-metastasis (TNM) classification), and overall survival of the breast cancer tissues were analyzed using Pearson's χ-square (χ²) test, Fisher's exact test, multivariate logistic regression and Kaplan-Meier survival analysis. Significantly higher expressions of pCHK2-Thr68 and pCDC25C-Ser216 were observed in the nucleus of the breast cancer cells compared to the paracancerous tissue (pCHK2-Thr68, 20.38% vs. 0%; pCDC25C-Ser216, 82.26% vs. 24.24%). The expression of pCHK2-Thr68 and pCDC25C-Ser216 in breast cancer showed a positive linear correlation ( = 0.026). High expression of pCHK2-Thr68 was associated with decreased patient survival ( = 0.001), but was not an independent prognostic factor. Our results suggest that pCHK2-Thr68 and pCDC25C-Ser216 play important roles in breast cancer and may be potential treatment targets.
检查点激酶2(CHK2)和细胞分裂周期蛋白25C(CDC25C)是参与DNA损伤反应途径的两种蛋白质,在维持基因组完整性方面发挥着重要作用。基因组不稳定是细胞异常分裂的主要标志之一,在大多数癌症中都会出现。在本研究中,我们确定了pCHK2-Thr68和pCDC25C-Ser216在乳腺癌中的功能性表达及其与乳腺癌生存的关系。通过免疫组织化学构建组织微阵列分析,以确定292例女性乳腺癌患者中pCHK2-Thr68和pCDC25C-Ser216的表达情况。使用Pearson卡方(χ²)检验、Fisher精确检验、多因素逻辑回归和Kaplan-Meier生存分析,分析了乳腺癌组织中蛋白质表达、临床病理因素(如人表皮生长因子受体2(HER 2)、肿瘤大小、肿瘤-淋巴结-转移(TNM)分类)与总生存之间的关系。与癌旁组织相比,在乳腺癌细胞核中观察到pCHK2-Thr68和pCDC25C-Ser216的表达显著更高(pCHK2-Thr68,20.38%对0%;pCDC25C-Ser216,82.26%对24.24%)。乳腺癌中pCHK2-Thr68和pCDC25C-Ser216的表达呈正线性相关( = 0.026)。pCHK2-Thr68的高表达与患者生存率降低相关( = 0.001),但不是独立的预后因素。我们的结果表明,pCHK2-Thr68和pCDC25C-Ser216在乳腺癌中发挥重要作用,可能是潜在的治疗靶点。