Liu Fang, Zhang Yuan, Lu Ming, Wang Cong, Li Qingbao, Gao Yongsheng, Mu Dianbin, Cao Yan, Li Miaomiao, Meng Xiangjiao
Department of Imaging, Shandong Medical College Jinan 250002, Shandong, China.
Department of Laboratory Medicine, Shandong Medical College Jinan 250002, Shandong, China.
Am J Transl Res. 2017 Mar 15;9(3):1392-1401. eCollection 2017.
Lung cancer is currently the leading cause of cancer-related death worldwide and it is important to identify the predictive and/or prognostic markers for the cancer. , a proliferative and multipotent biomarker has been reported to be associated with prognosis in non-small cell lung cancer (NSCLC) in a few studies. In the present study, we retrospectively recruited 153 patients with NSCLC. protein expression in tumor samples was determined by immunohistochemistry staining. expression was related with tumor differentiation (P=0.036), lymphatic metastasis (N stage, P=0.011), and p-TNM stage (P=0.013), while there was no significant association between expression level and age, smoking habits, gender, histologic type, and T stage. was an independent prognostic factor for overall survival in NSCLC with an adjusted hazard ratio of 2.701 (95% CI, 1.616-4.513, P<0.001) after controlling the confounding factors. Then we determined the effects of on cell proliferation, colony formation, invasion, and apoptosis by knockout of with a new developed method, CRISPR/Cas9 mediated genome editing. It was observed that knockout of caused enhancement of cancer cell apoptosis and inhibition of cell proliferation, colony formation, and invasion in A549 and H1299 cell lines. Furthermore, we examined the expression of epithelial-mesenchymal transition (EMT) related biomarkers such as E-cadherin and Vimentin in -depleted lung cancer cells and knockout of was found to inhibit EMT, suggesting the involvement of mediated EMT signaling in lung cancer. The finding above demonstrated that might serve as a prognostic factor and therapeutic target in NSCLCs.
肺癌是目前全球癌症相关死亡的主要原因，识别该癌症的预测和/或预后标志物很重要。在一些研究中，一种增殖性和多能生物标志物已被报道与非小细胞肺癌（NSCLC）的预后相关。在本研究中，我们回顾性招募了153例NSCLC患者。通过免疫组织化学染色测定肿瘤样本中的蛋白表达。表达与肿瘤分化（P = 0.036）、淋巴转移（N分期，P = 0.011）和p-TNM分期（P = 0.013）相关，而表达水平与年龄、吸烟习惯、性别、组织学类型和T分期之间无显著关联。在控制混杂因素后，是NSCLC总生存的独立预后因素，调整后的风险比为2.701（95%CI，1.616 - 4.513，P < 0.001）。然后我们用一种新开发的方法CRISPR/Cas9介导的基因组编辑敲除来确定对细胞增殖、集落形成、侵袭和凋亡的影响。观察到敲除导致A549和H1299细胞系中癌细胞凋亡增强，细胞增殖、集落形成和侵袭受到抑制。此外，我们检测了-缺失的肺癌细胞中上皮-间质转化（EMT）相关生物标志物如E-钙黏蛋白和波形蛋白的表达，发现敲除可抑制EMT，提示介导的EMT信号通路参与肺癌发生。上述发现表明可能作为NSCLC的预后因素和治疗靶点。
