摘要
目的基于前列腺素内过氧化物合成酶2(PTGS2)在结肠癌中的表达及预后分析,探讨并验证PTGS2影响结肠癌患者预后的潜在分子机制。方法从TCGA、HPA、UALCAN等数据库收集泛癌的转录组和蛋白质组学数据,并结合肿瘤患者的分期分型、生存时间等临床数据,分析PTGS2基因的表达模式和预后价值。基于基因集合富集分析(GSEA)鉴定在PTGS2高表达患者中显著激活的生物学功能,并以结肠癌细胞系SW480为例,进行体外验证。构建PTGS2过表达细胞株,使用CCK8法测定对细胞增殖的影响;使用不同浓度H 2O 2形成梯度氧化胁迫,检测细胞抗氧化能力的变化;并通过蛋白质免疫印迹初步验证其调控机制。结果PTGS2的转录水平和表达水平在结肠癌患者中均显著上调(P<0.05),且PTGS2的表达升高与患者的死亡风险升高相关(P<0.05)。数据分析和体外实验表明过表达PTGS2可能通过激活mTOR通路促进结肠癌细胞增殖;并通过上调氧化应激调控蛋白SOD2、NRF2调控细胞抗氧化能力。结论PTGS2是一个潜在的结肠癌危险因素,其表达水平升高促进细胞增殖,增强细胞抗氧化能力,并与结肠癌患者不良预后相关。
Objective To investigate the effect and potential molecular mechanism of PTGS2 on the prognosis of colon cancer patients.Methods The transcriptomic and proteomic data of pan-cancer were collected from TCGA,HPA,UALCAN and other databases,and the expression pattern and prognostic value of PTGS2 were analyzed by combining the clinical data such as staging,histology,survival time and so on.Based on GSEA,the biological functions which were significantly activated in patients with high expression of PTGS2 were identified and the colon cancer cell line SW480 was used as an example for in vitro validation.PTGS2 over-expressing cell strains were constructed,and the effect on cell proliferation was determined by CCK8 method.Different concen-trations of H 2O 2 were used to form gradient oxidative stress,and the changes in cell antioxidant capacity were detected.The regulatory mechanism was preliminarily verified by Western blot.Results The transcription and expression of PTGS2 were found to be significantly up-regulated in colon cancer patients(P<0.05),and the increased expression of PTGS2 was associated with an increased mortality risk(P<0.05).Data analysis and in vitro experiments showed that over-expression of PTGS2 may promote the proliferation of colon cancer cells by activating the mTOR pathway.The antioxidant effect of cells was regulated by up-regulating oxidative stress regulatory proteins SOD2 and NRF2.Conclusions PTGS2 is a potential risk factor for colon cancer and its over-expression promotes cell proliferation,enhances cell antioxidant effect and is associated with poor prognosis of colon cancer patients.
作者
贺旸知歌
姜旭
张志文
龚依伊
HE Yangzhige;JIANG Xu;ZHANG Zhiwen;GONG Yiyi(Center for Bioinformatics,Peking Union Medical College Hospital,CAMS&PUMC,Beijing 100730,China;Center for Biomarker,Peking Union Medical College Hospital,CAMS&PUMC,Beijing 100730,China;Department of Pathology,Peking Union Medical College Hospital,CAMS&PUMC,Beijing 100730,China)
出处
《基础医学与临床》
CAS
2024年第11期1522-1529,共8页
Basic and Clinical Medicine
基金
北京市自然科学基金(7244392,7242106)
国家自然科学基金(82100942)
中央高水平医院临床科研专项经费(2022-PUMCH-A-202)。
