本文選題：磷酸甘油酸激酶1 + Beclin1　； 參考：《北京協(xié)和醫(yī)學(xué)院》2017年博士論文

【摘要】：背景肺癌目前仍是我國乃至世界上發(fā)生率和死亡率都位居前列的惡性腫瘤。肺癌總體5年生存率僅為18%,原因部分由于診斷時(shí)中后期肺癌所占比例較高,而此時(shí)生存率極低。因此早診早治是提升肺癌生存率的有效手段,目前的低劑量CT的篩查方式雖然能提供有效方法進(jìn)行早期診斷,但仍有所不足。目前分子分型及靶向治療在腫瘤診斷治療方面有極大地貢獻(xiàn),特別在肺腺癌治療方面有了長足的進(jìn)步。磷酸甘油酸激酶1(PGK1)作為參與糖酵解過程的重要激酶,在多種腫瘤中起到促癌作用,進(jìn)來發(fā)現(xiàn)其特殊的K388位點(diǎn)的乙酰化能夠磷酸化Beclin1 S30的磷酸化從而進(jìn)一步促進(jìn)PIK3C3-PtdIns3P通路引導(dǎo)的自噬過程,可能可以從某些方面解釋腫瘤的形成發(fā)展過程,具有成為腫瘤標(biāo)志物的潛力。目的評(píng)估PGK1 Ac-K388、Beclin1 pS30及其他與PGK1相關(guān)的參與自噬通路的蛋白在肺腺癌TNM分期及生存時(shí)間上的臨床價(jià)值。方法我們通過TCGA數(shù)據(jù)庫搜索與PGK1表達(dá)相關(guān)的蛋白,并驗(yàn)證PGK1、Beclinl與篩查出的蛋白在腫瘤中的表達(dá)以及與肺腺癌分期及預(yù)后的關(guān)系,之后在90對肺腺癌組織及其配對的正常組織的組織芯片上應(yīng)用免疫組化的方法進(jìn)行進(jìn)一步驗(yàn)證。結(jié)果我們通過TCGA肺腺癌數(shù)據(jù)庫找到了兩個(gè)與PGK1表達(dá)相關(guān)的蛋白:ATG12與INPP5A,四種蛋白在肺腺癌組織及正常肺組織之間表達(dá)差異具有統(tǒng)計(jì)學(xué)意義,且ATG12與INPP5A對不同表達(dá)水平對生存時(shí)間造成的差異具有顯著性意義。之后我們在90對肺腺癌患者的肺腺癌組織與正常肺組織的組織芯片上用免疫組化進(jìn)行驗(yàn)證,結(jié)果顯示PGKAc-K388、Beclin1 pS30、ATG12在肺腺癌組織及正常肺組織之間表達(dá)差異,且Beclin1 S30磷酸化水平可以作為預(yù)后的保護(hù)性因素。結(jié)論P(yáng)GK1 Ac-K388與Beclin1 pS30不同水平在腫瘤大小、腫瘤分期上的差異具有統(tǒng)計(jì)學(xué)意義,且Beclin1 S30磷酸化水平可以作為肺腺癌的預(yù)后因素,而INPP5A表達(dá)水平在腫瘤家族史、是否存在淋巴結(jié)侵犯以及不同腫瘤分期之間的差異具有統(tǒng)計(jì)學(xué)意義。
[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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R734.2

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