Effect Of Inprotant Glycolytic Kinsase(PGK1)in Lung Adenocarcinoma

BackgroundNowadays,lung cancer has become one of the most common malignancy in china and the world.The 5 year survival rate of lung cancer is only 18%,partly due to the high percentage of distant stage cases when they were diagnosed.Early diagnosis and early treatment is effective to elevate the survival rate of lung cancer,but low dose CT is not that sufficient.Molecular classification and target therapy have greatly improved the diagnosis and treatment of many tumor types especially lung adenocarcinoma.Phosphoglycerate kinase 1,as an important kinase joining the glycolysis,plays an important role in promoting tumor in many cancer types.Recently,we found that specially acetylating K388 of PGK1 can phosphate Beclinl S30 and promoting PIK3C3-PtdIns3Pinducing autophagia,which can partly explain the mechanism of tumor formation and progression.In a word,PGK1 has the potential to be a tumor biomarker of lung adenocarcinoma.ObjectiveIn this study,we validated the clinical significance of PGK1 Ac-K388 and its relating proteins,and varified whether they cound act as a ideal biomarker in lung adenocarcinoma staging and prognosis forcasting.MethodsWe use TCGA lung adenocarcinoma database to seek for PGK1 relating proteins,and confirming the clinical significance of PGK1、Beclinl and relating proteins by immunohistochemistry of tissue microarray of 90 lung adnocarcinoma samples with matching normal lung tissue.ResultsWe finally find ATG12 and INPP5A as two proteins in correlation with PGK1 mRNA level in TCGA lung adenocarcinoma database.These four proteins cause significant difference between lung adenocarcinoma and normal lung tissue.The different mRNA level of ATG12 and INPP5A makes significant difference among survival time.On the other side,we detect the expression of four facors by immunohistochemisry in tissue microarray of 90 lung adnocarcinoma samples with matching normal lung tissue.Finally.we confirm the signature difference in four proteins expression level among tissues between lung adenocarcinoma and normal lung and that phosphorylation level of Beclinl can act as the independent prognostic protective factor in lung adenocarcinoma patients.Conclusions:The different acetylation level ofPGK1 K388 and phosphorylation level of Beclinl cause significant difference between tumor burden and tumor stage,and phosphorylation level of Beclinl can act as the independent prognostic factor in lung adenocarcinoma.There exists different expression level of INPP5A among different family history,lymph note metastasis and tumor stage.