Ren K, Qian D, Wang Y W, Pang Q S, Zhang W C, Yuan Z Y, Wang P
Department of Radiation Oncology, Cancer Institute and Hospital of Tianjin Medical University, National Clinical Research Center of Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center of Cancer, Tianjin 300060, China.
Zhonghua Zhong Liu Za Zhi. 2018 Jan 23;40(1):21-27. doi: 10.3760/cma.j.issn.0253-3766.2018.01.004.
To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells. A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry. Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference (=0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; =0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results (=0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients(<0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast, knockdown NS1-BP in KYSE510 cells induced c-Myc expression, increased cell proliferation and repressed apoptosis. NS1-BP is an independent favorable prognostic factor in ESCC. It inhibits cell proliferation and enhances cell apoptosis via repressing c-Myc. Targeting NS1-BP may be a new therapeutic strategy for ESCC patients.
探讨NS1-BP表达在食管鳞状细胞癌(ESCC)患者中的临床意义,并研究NS1-BP在ESCC细胞增殖和凋亡中的作用。选取98例ESCC患者的98个肿瘤组织和30个癌旁正常组织作为研究组和对照组,这些样本于2002年至2008年在中山大学肿瘤防治中心收集。此外,选取天津医科大学肿瘤研究所和医院收集的46例ESCC组织作为验证组。采用免疫组织化学法检测黏膜NS1-BP的表达。采用Kaplan-Meier曲线和log-rank检验分析生存率。采用多因素Cox比例风险模型分析预后因素。此外,通过瞬时转染在ESCC细胞中过表达或敲低NS1-BP。采用蛋白质印迹法检测c-Myc的蛋白水平。采用MTT法和流式细胞术分析细胞活力和凋亡情况。在所有检测样本中,30例非肿瘤性正常食管组织中有9例(30.0%)NS1-BP表达下调,144例ESCC组织中有85例(59.0%)NS1-BP表达下调,差异有统计学意义(P=0.012)。在研究组中,NS1-BP高表达组的三年无病生存率(53.2%)显著高于NS1-BP低表达组(27.6%;P=0.009)。在验证组中,NS1-BP高水平组和低水平组的三年无病生存率分别为57.8%和25.5%,结果相似(P=0.016)。重要的是,多因素分析显示NS1-BP低表达是ESCC患者放化疗敏感性和无病生存时间缩短的独立预测因素(均P<0.05)。此外,在TE-1细胞中过表达NS1-BP可抑制c-Myc表达,抑制细胞增殖并促进凋亡。相反,在KYSE510细胞中敲低NS1-BP可诱导c-Myc表达,增加细胞增殖并抑制凋亡。NS1-BP是ESCC的独立有利预后因素。它通过抑制c-Myc抑制细胞增殖并增强细胞凋亡。靶向NS1-BP可能是ESCC患者的一种新治疗策略。