DTX3L在结直肠癌中的表达及其对结直肠癌细胞耐药性的影响  

Expression of DTX3L in colorectal cancer and its effect on drug resistance of colorectal cancer cells

作　　者：李志鹏 耿良栋 刘继斌 王兴丹 刁迅 崔惊鸿 崔小鹏[4] LI Zhipeng;GENG Liangdong;LIU Jibin;WANG Xingdan;DIAO Xun;CUI Jinghong;CUI Xiaopeng(Medical College of Nantong University,Jiangsu 226001;Cancer Research Institute,Tumor Hospital Affiliated to Nantong University/Nantong Tumor Hospital;Department of Radiotherapy,Tumor Hospital Affiliated to Nantong University/Nantong Tumor Hospital;Department of General Surgery,Affiliated Hospital of Nantong University)

机构地区：[1]南通大学医学院,江苏226001 [2]南通大学附属肿瘤医院/南通市肿瘤医院肿瘤研究所 [3]南通大学附属肿瘤医院/南通市肿瘤医院放疗科 [4]南通大学附属医院普通外科

出　　处：《交通医学》2024年第2期111-115,共5页Medical Journal of Communications

基　　金：江苏省研究生科研与实践创新计划项目(SJCX22_1629,SJCX22_1637);南通市科技局课题(JC22022009,JC22022027);南通市卫生健康委员会课题(MS2023056)。

摘　　要：目的:分析DTX3L蛋白在结直肠癌(colorectal cancer,CRC)中的表达及其对结直肠癌细胞耐药性的影响。方法:收集南通大学附属医院结直肠癌组织及配对的癌旁正常结肠组织病理标本330例,采用免疫组织化学染色检测癌组织及其癌旁正常结肠组织中DTX3L表达水平,分析DTX3L表达水平与患者临床病理特征之间的关系。绘制Kaplan-Meier生存曲线分析DTX3L表达与患者预后的关系。以慢病毒转染构建DTX3L敲低的人结肠癌细胞系(CACO-2),将倍数稀释的奥沙利铂加入DTX3L敲低组和NC组CACO-2细胞中,CCK8法检测奥沙利铂对两组细胞的半抑制浓度(IC50)。结果:结直肠癌组织中DTX3L表达水平显著高于癌旁正常结肠组织,差异有统计学意义(P<0.05)。DTX3L表达水平与患者肿瘤T分期、N分期、pTNM分期有关(P<0.05)。DTX3L高表达组患者中位生存时间(median survival time,MST)45.5个月,小于DTX3L低表达组的55.2个月,差异有统计学意义(P<0.05)。术后接受奥沙利铂化疗患者中DTX3L高表达与不良预后相关(HR=1.81,95%CI:1.05~3.11,P<0.05)。细胞实验结果显示,DTX3L敲低组奥沙利铂IC50为8.14 mg/mL,小于NC组的13.36 mg/mL。结论:结直肠癌患者癌组织中DTX3L表达上调与不良预后相关,敲低DTX3L可增加CRC细胞对奥沙利铂的敏感性,DTX3L可能成为CRC患者的预后指标和分子治疗的新靶点。Objective:To analyze the expression of DTX3L protein in colorectal cancer(CRC)and its impact on drug resistance of colorectal cancer cells.Methods:A total of 330 CRC tissue and adjacent normal colon tissue pathological specimens were collected from Affiliated Hospital of Nantong University.Immunohistochemical staining was used to detect the expression levels of DTX3L in cancerous and adjacent normal colon tissues,and the relationship between DTX3L expression and clinical pathological characteristics of patients was analyzed.Kaplan-Meier survival curves were plotted to analyze the relationship between DTX3L expression and the prognosis of CRC patients.A human colon cancer cell line(CACO-2)with DTX3L knockdown was constructed using lentiviral transfection.Diluted oxaliplatin was added to CACO-2 cells both in the DTX3L knockdown group and the NC group,and the half-maximal inhibitory concentration(IC50)values of oxaliplatin were detected using the CCK8 method.Results:The expression level of DTX3L in CRC tissue was significantly higher than that in adjacent normal colon tissue,with a statistical difference(P<0.05).The expression level of DTX3L was related to the patients′tumor T stage,N stage,and pTNM stage(P<0.05).The median survival time(MST)of patients in the high DTX3L expression group was 45.5 months,which was shorter than the 55.2 months in the low DTX3L expression group,with a statistical difference(P<0.05).In patients who underwent postoperative oxaliplatin chemotherapy,high expression of DTX3L was associated with poor prognosis(HR=1.81,95%CI:1.05~3.11,P<0.05).Cellular experiments showed that the oxaliplatin half-maximal inhibitory concentration(IC50)for the DTX3L knockdown group was 8.14 mg/mL,lower than 13.36 mg/mL for the NC group.Conclusion:Upregulation of DTX3L expression in cancerous tissues of CRC patients is associated with poor prognosis.Knockdown of DTX3L can increase the sensitivity of CRC cells to oxaliplatin,and DTX3L may become a new prognostic marker and molecular therapeutic target for CRC pa

关 键 词：结直肠癌 DTX3L 预后 奥沙利铂 耐药性 

分 类 号：R735.35[医药卫生—肿瘤]