Objective:To investigate the expression changes of farnesoid X receptor (FXR) in the evolution of normal intestinal mucosa, colorectal adenoma (CRA) and colorectal cancer (CRC), and the correlation of FXR expression with clinicopathological features and prognosis of patients with colorectal tumors.Methods:The UALCAN website tool was used to analyze the expression level of FXR gene transcripts of CRC and normal colorectal tissues in The Cancer Genome Atlas (TCGA) database. The patients undergoing colonoscopy and treatment in the Aerospace Center Hospital from January 2019 to September 2020 were selected, and the immunohistochemistry was used to detect the expression of FXR protein in 100 CRA tissues, 47 CRC tissues and 11 normal colonic mucosal tissues from healthy people (healthy control). Combining with clinical data, the relationship between FXR protein expression and clinicopathological characteristics of patients with colorectal tumors was analyzed. According to the Kaplan-Meier Plotter online database, the median expression level of FXR gene transcripts in CRC patients was analyzed, and the patients were divided into FXR low-expression group and high-expression group, the relationship between the expression of FXR gene and prognosis of CRC patients was investigated.Results:The analysis of data from TCGA database showed that the expression level of FXR gene transcripts in CRC tissues was lower than that in normal colorectal tissues ( P < 0.01). Immunohistochemical examination of the collected tissues showed that the positive rate of FXR protein gradually decreased from the cecum to the rectum. The positive rates of FXR protein in healthy control, CRA patients and CRC patients were 90.9% (10/11), 24.0% (24/100), 6.3% (3/47), and the difference was statistically significant ( χ2 = 35.56, P < 0.01); the positive rate of FXR protein in cancer tissues from CRC patients was lower than that in normal tissues adjacent to cancer [6.3% (3/47) vs. 65.2% (15/23)], and the difference was statistically significant ( χ2 = 27.98, P < 0.01). There was no statistical difference in the positive rate of FXR among CRA patients with different gender, age, maximum diameter of adenoma, and aggression (all P > 0.05). There was also no statistical difference in the positive rate of FXR among CRC patients with different gender, age, tumor site, maximum diameter of tumor, degree of differentiation, TNM staging, and vascular tumor thrombus (all P > 0.05). According to the survival analysis of Kaplan-Meier Plotter online database, the recurrence-free survival of CRC patients with high expression of FXR was better than that of patients with low expression of FXR ( P = 0.003). Conclusions:The expression level of FXR gradually decreases in the intestinal tissues of healthy people, CRA patients and CRC patients. The prognosis of CRC patients with low FXR expression is poor.
目的 检测肿瘤坏死因子相关凋亡诱导配体(TRAIL)对胃癌细胞的杀伤作用及其受体在胃癌细胞中的表达情况,评估TRAIL信号在胃癌治疗中的可行性.方法 研究选取11株胃癌细胞进行实验,采用实时荧光定量PCR方法检测胃癌细胞中TRAIL相关受体(DR4、DR5、DcR1、DcR2)mRNA表达.采用Cell Counting Kit-8(CCK-8)法检测TRAIL抑制胃癌细胞生长,Annexin V/PI双染色法测定TRAIL诱导细胞凋亡,Western blot检测TRAIL介导Caspase裂解.结果 死亡受体DR4、DR5在11株胃癌细胞内普遍高表达,表达水平显著高于诱骗受体DcR1、DcR2.TRAIL对9株胃癌细胞有不同程度的生长抑制作用,SNU-16、NUGC3、NCI-N87和SNU-1灵敏度最高,抑制作用呈时间和剂量依赖性.TRAIL通过诱导细胞凋亡发挥肿瘤杀伤作用,低浓度TRAIL(200 ng/ml)作用24 h后50%以上细胞发生凋亡.Caspase-3、-8、-9和PARP的裂解水平与凋亡程度相关.结论 TRAIL对胃癌细胞具有不同程度的生长抑制和凋亡诱导作用,在胃癌中具有潜在应用价值.
目的 评估2014年《中国早期胃癌筛查及内镜诊治共识意见》关于胃癌高危人群筛查在不同地区的适用性及有效性.方法 选取2018年1月至2018年6月就诊于安阳市人民医院和航天中心医院消化内科的患者,通过问卷调查方式采集胃癌相关高危因素信息,根据《共识意见》分为高危组及低危组,经胃镜及病理检查确认,比较两组患者胃癌、癌前疾病及癌前病变的检出情况,并分析胃癌高危因素.结果 384例患者根据《共识意见》分为胃癌高危组265例(69.0%)、低危组119例(31.0%).高危组患者胃癌、癌前病变检出率均为9.4%(25/265),显著高于低危组胃癌(1.7%,2/119)和癌前病变检出率(3.4%,4/119)(P<0.01),《共识意见》对胃癌的敏感性为92.6%,特异性为32.8%;高危组患者问卷调查中危险因素符合项数主要体现为2~3项,其中胃癌前疾病史及不良饮食习惯是胃癌发病的独立危险因素.结论 2014年《中国早期胃癌筛查及内镜诊治共识意见》在不同地区医院内筛查胃癌高危人群的适用性相同,其敏感性高而特异性及总符合率较低.与其他高危因素相比,既往癌前疾病史、吃饭速度快及饮食不规律与胃部疾病相关性更高.