糖酵解中重要激酶（PGK1）在肺腺癌中的应用

发布时间：2018-07-09 15:14

本文选题：磷酸甘油酸激酶1 + Beclin1　；参考：《北京协和医学院》2017年博士论文

【摘要】：背景肺癌目前仍是我国乃至世界上发生率和死亡率都位居前列的恶性肿瘤。肺癌总体5年生存率仅为18%,原因部分由于诊断时中后期肺癌所占比例较高,而此时生存率极低。因此早诊早治是提升肺癌生存率的有效手段,目前的低剂量CT的筛查方式虽然能提供有效方法进行早期诊断,但仍有所不足。目前分子分型及靶向治疗在肿瘤诊断治疗方面有极大地贡献,特别在肺腺癌治疗方面有了长足的进步。磷酸甘油酸激酶1(PGK1)作为参与糖酵解过程的重要激酶,在多种肿瘤中起到促癌作用,进来发现其特殊的K388位点的乙酰化能够磷酸化Beclin1 S30的磷酸化从而进一步促进PIK3C3-PtdIns3P通路引导的自噬过程,可能可以从某些方面解释肿瘤的形成发展过程,具有成为肿瘤标志物的潜力。目的评估PGK1 Ac-K388、Beclin1 pS30及其他与PGK1相关的参与自噬通路的蛋白在肺腺癌TNM分期及生存时间上的临床价值。方法我们通过TCGA数据库搜索与PGK1表达相关的蛋白,并验证PGK1、Beclinl与筛查出的蛋白在肿瘤中的表达以及与肺腺癌分期及预后的关系,之后在90对肺腺癌组织及其配对的正常组织的组织芯片上应用免疫组化的方法进行进一步验证。结果我们通过TCGA肺腺癌数据库找到了两个与PGK1表达相关的蛋白:ATG12与INPP5A,四种蛋白在肺腺癌组织及正常肺组织之间表达差异具有统计学意义,且ATG12与INPP5A对不同表达水平对生存时间造成的差异具有显著性意义。之后我们在90对肺腺癌患者的肺腺癌组织与正常肺组织的组织芯片上用免疫组化进行验证,结果显示PGKAc-K388、Beclin1 pS30、ATG12在肺腺癌组织及正常肺组织之间表达差异,且Beclin1 S30磷酸化水平可以作为预后的保护性因素。结论PGK1 Ac-K388与Beclin1 pS30不同水平在肿瘤大小、肿瘤分期上的差异具有统计学意义,且Beclin1 S30磷酸化水平可以作为肺腺癌的预后因素,而INPP5A表达水平在肿瘤家族史、是否存在淋巴结侵犯以及不同肿瘤分期之间的差异具有统计学意义。
[Abstract]:Background Lung cancer is still one of the leading malignant tumors in China and the world. The overall 5-year survival rate of lung cancer was only 18%, partly due to the high proportion of lung cancer in the middle and late stage of diagnosis, but the survival rate was very low. Therefore, early diagnosis and early treatment is an effective means to improve the survival rate of lung cancer. Although the current screening method of low dose CT can provide an effective method for early diagnosis, it is still insufficient. Molecular typing and targeted therapy have contributed greatly to the diagnosis and treatment of tumor, especially in the treatment of lung adenocarcinoma. Phosphoglycerate kinase 1 (PGK1), as an important kinase involved in glycolysis, plays a role in the promotion of cancer in many tumors. It was found that the acetylation of its special K388 site could phosphorylate the phosphorylation of Beclin1 S30, thus further promoting the autophagy induced by the PIK3C3-PtdIns3P pathway, which might explain the process of tumor formation and development in some ways. It has the potential to be a tumor marker. Objective to evaluate the clinical value of PGK1Ac-K388Beclin1 pS30 and other PGK1-related proteins involved in autophagy pathway in TNM staging and survival time of lung adenocarcinoma. Methods the expression of PGK1 protein was searched by TCGA database, and the relationship between PGK1 Beclinl and the screened protein in tumor and the stage and prognosis of lung adenocarcinoma was examined. The immunohistochemical method was used to further verify the tissue microarray of lung adenocarcinoma and its matched normal tissues. Results through the TCGA lung adenocarcinoma database, we found two proteins related to the expression of PGK1: ATG12 and INPP5A.The expression of the four proteins in lung adenocarcinoma and normal lung tissues was statistically significant. ATG12 and INPP5A had significant difference in survival time between different expression levels. Then we examined the expression of PGKAc-K388Beclin1 pS30 ATG12 in lung adenocarcinoma tissue and normal lung tissue by immunohistochemistry in 90 cases of lung adenocarcinoma and normal lung tissue, the results showed that the expression of PGKAc-K388pS30 ATG12 in lung adenocarcinoma tissue and normal lung tissue was different from that in normal lung tissue. And the phosphorylation level of Beclin 1 S 30 may be a protective factor for prognosis. Conclusion different levels of PGK1Ac-K388 and Beclin1 pS30 have statistical significance in tumor size and tumor staging. Beclin-1 S30 phosphorylation level may be a prognostic factor for lung adenocarcinoma, while INPP5A expression level is in the family history of the tumor. There were statistically significant differences in lymph node involvement and different tumor stages.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R734.2

【相似文献】