基础医学与临床 ›› 2024, Vol. 44 ›› Issue (11): 1522-1529.doi: 10.16352/j.issn.1001-6325.2024.11.1522

• 研究论文 • 上一篇    下一篇

PTGS2调控细胞增殖及抗氧化能力影响结肠癌患者预后

贺旸知歌1, 姜旭2, 张志文3, 龚依伊2*   

  1. 中国医学科学院 北京协和医学院 北京协和医院 1.生物信息技术平台;
    2.生物标志物平台;
    3.病理科, 北京 100730
  • 收稿日期:2024-08-05 修回日期:2024-09-12 出版日期:2024-11-05 发布日期:2024-10-31
  • 通讯作者: *gongyy5411@163.com
  • 基金资助:
    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)

PTGS2 affects prognosis of colon cancer patients through regulation of cell proliferation and antioxidant capacity

HE Yangzhige1, JIANG Xu2, ZHANG Zhiwen3, GONG Yiyi2*   

  1. 1. Center for Bioinformatics;
    2. Center for Biomarker;
    3. Department of Pathology, Peking Union Medical College Hospital, CAMS & PUMC, Beijing 100730, China
  • Received:2024-08-05 Revised:2024-09-12 Online:2024-11-05 Published:2024-10-31
  • Contact: *gongyy5411@163.com

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H2O2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。

关键词: 结肠癌, 前列腺素内过氧化物合成酶2(PTGS2), 泛癌, 增殖, 抗氧化能力

Abstract: 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 H2O2 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.

Key words: colon cancer, prostaglandin-endoperoxide synthase 2(PTGS2), prognosis, proliferation, antioxidant capacity

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