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The Role Of PTGDS In Non-small Cell Lung Cancer

Posted on:2018-02-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:L P HeFull Text:PDF
GTID:1364330542966627Subject:Respiratory medicine
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Background:Whether at home or abroad,the incidence and mortality of lung cancer are at the forefront in all malignant tumors.The most common type of lung cancer is non-small cell lung cancer(NSCLC),accounting for about 85 percent.According to histopathological types,NSCLC can be divided into lung adenocarcinoma,lung squamous cell carcinoma and large cell lung cancer.Lung adenocarcinoma and lung squamous cell carcinoma are the two most common histologic types of NSCLC.In patients with early stage of NSCLC,the five years survival rate can reach about forty percent after surgical treatment.However,about seventy percent NSCLC patients have been advanced or have associated local or distant metastasis,missing the best time for surgical resection,leading to poor prognosis.Therefore,it is necessary to explore and study the markers and the genes involved in targeted therapy of NSCLC.Methods:Primarily,the expression of prostaglandin D2 synthetase in NSCLC was studied through GEO database.Then the result was verified by a tissue microarray treated with immunohistochemical staining.Based on the two results of GEO database and tissue microarray,the protein expression of prostaglandin D2 synthetase in lung adenocarcinoma and lung squamous cell carcinoma was determined.Next,the prostaglandin D2 synthetase protein expression was overexpressed in A549 and Calu-3 cell lines to study the biological behavioristic transformation of lung adenocarcinoma cells.Lastly,the protein expression differences of some related proteins was tested through western blot to explore its molecular mechanism.Results:The results of GEO database and tissue microarray showed that prostaglandin D2 synthetase was down-regulated in both lung adenocarcinoma and lung squamous cell carcinoma,but no protein expression difference was found between them.Prostaglandin D2 synthetase protein expression was related to the tumor stage and prognosis of lung adenocarcinoma,but not related to the tumor stage and prognosis of lung squamous cell carcinoma.The result of cell experiment revealed that after prostaglandin D2 synthetase overexpression,the invasion ability of A549 and Calu-3 cells was significantly inhibited,and the expressions of MAPK signal pathway key proteins P38,ERK and JNK were significantly decreased.Conclusions:(1)The present study found that prostaglandin D2 synthase expression was down-regulated in both lung adenocarcinoma and lung squamous cell carcinoma,but no protein expression difference was found between them;(2)Prostaglandin D2 synthetase protein expression was related to the tumor stage and prognosis of lung adenocarcinoma,but not related to the tumor stage and prognosis of lung squamous cell carcinoma,prostaglandin D2 synthase may play a more critical role in lung adenocarcinoma;(3)After prostaglandin D2 synthetase overexpression,the invasion ability of A549 and Calu-3 cells was significantly inhibited,and the expressions of MAPK signal pathway key proteins P38,ERK and JNK were significantly decreased.The inhibitory effect of prostaglandin D2 synthase on the invasion of lung adenocarcinoma may be mediated by its inhibition on the MAPK signaling pathway.
Keywords/Search Tags:Non-small
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