CYP2亚家族成员在结肠癌中的表达水平及功能验证研究  

Expression Levels and Functional Verification of Members of the CYP2 Subfamily in Colon Cancer

作　　者：蒋琴 周航宇 魏远 王宏 Jiang Qin;Zhou Hangyu;Wei Yuan;Wang Hong(Department of Human Anatomy,Histology and Embryology,School of Basic Medicine,Sichuan College of Traditional Chinese Medicine,Mianyang 621000,Sichuan,China;Department of General Surgery,the First People's Hospital of Mianyang(i.e.Mianyang 404 Hospital),Mianyang 621000,Sichuan,China;Department of Medical Imaging,the First People's Hospital of Mianyang(i.e.Mianyang 404 Hospital),Mianyang 621000,Sichuan,China;Department of Interventional Radiology,the First People's Hospital of Mianyang(i.e.Mianyang 404 Hospital),Mianyang 621000,Sichuan,China)

机构地区：[1]四川中医药高等专科学校基础医学部人体解剖学与组织胚胎学教研室,四川绵阳621000 [2]绵阳市第一人民医院/绵阳四○四医院普外科,四川绵阳621000 [3]绵阳市第一人民医院/绵阳四○四医院医学影像科,四川绵阳621000 [4]绵阳市第一人民医院/绵阳四○四医院介入放射科,四川绵阳621000

出　　处：《肿瘤预防与治疗》2024年第12期1015-1023,共9页Journal of Cancer Control And Treatment

基　　金：绵阳市卫健委2022年科研课题补助项目(编号:202205)。

摘　　要：目的:本研究利用公共数据库结合细胞功能学实验,筛选结肠癌中呈差异表达的CYP450超家族2亚家族基因,系统分析CYP2家族基因在结肠癌中的表达情况及功能作用。方法:利用TCGA数据库,筛选结肠癌中呈差异表达的CYP2家族基因;运行R包进行预后和功能富集分析;EdU实验检测过表达CYP2J2对结肠癌细胞增殖的影响;划痕愈合和Transwell小室实验检测过表达CYP2J2对结肠癌细胞迁移的影响。结果:CYP2J2、CYP2C18、CYP2U1和CYP2D6在结肠癌中表达水平均显著降低;CYP2S1和CYP2W1表达水平均显著升高(均P<0.01)。CYP2J2低表达组患者和CYP2C18低表达组患者总生存期均显著缩短(均P<0.01)。CYP2J2和CYP2C18表达水平降低均是结肠癌早期发生的事件。KEGG结果显示,CYP2J2及其相关基因与细胞外基质-受体相互作用、黏着斑等信号通路有关。细胞学实验表明,过表达CYP2J2显著抑制结肠癌细胞增殖和细胞迁移(均P<0.01)。结论:低表达CYP2J2结肠癌患者和低表达CYP2C18结肠癌患者预后不良;过表达CYP2J2能够显著抑制结肠癌细胞增殖和迁移,提示CYP2J2可能是一个潜在的结肠癌预后标志物和治疗靶标。Objective: To screen the differentially expressed CYP2 family genes in colon carcinoma through public databases and cell functional experiments, and systematically analyze the expression and functions of CYP2 family genes in colon carcinoma.Methods: The Cancer Genome Atlas database was used to identify the differentially expressed genes(DEGs) in CYP2 subfamily in colon carcinoma. The R package was run for prognosis and gene function enrichment analyses. EdU was applied to detect the effect of overexpression of CYP2J2 on cell proliferation in colon carcinoma, and scratch healing and transwell chamber assays were applied to detect the effect of overexpression of CYP2J2 on cell migration in colon carcinoma.Results: CYP2J2, CYP2C18, CYP2U1 and CYP2D6 were down-regulated(P<0.01) in colon carcinoma, whereas CYP2S1 and CYP2W1 were up-regulated(P<0.01). The lower expressions of CYP2J2 and CYP2C18 were related to worse prognosis of colon carcinoma patients(P<0.01). Decreased expressions of CYP2J2 and CYP2C18 were both early events during the progression of colon carcinoma.KEGG results showed that CYP2J2 was related to signaling pathways such as extracellular matrix-receptor interaction and focal adhesion. Moreover, cytological experiments revealed that overexpression of CYP2J2 significantly inhibited the proliferation and migration abilities of colon carcinoma cells(P<0.01).Conclusion: Low expressions of CYP2J2 and CYP2C18 were related to the worse prognosis of colon carcinoma patients, and overexpression of CYP2J2 could inhibit the proliferation and migration abilities of colon carcinoma cells, suggesting that CYP2J2 might be a potential prognostic marker and therapeutic target of colon carcinoma.

关 键 词：CYP2J2 结肠癌 公共数据 细胞迁移 

分 类 号：R735.7[医药卫生—肿瘤]