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Significance Of High PD-L1 Expression In Nasopharyngeal Carcinoma And Its Mechanism Exploration

Posted on:2020-10-09Degree:MasterType:Thesis
Country:ChinaCandidate:H ZhangFull Text:PDF
GTID:2404330578967565Subject:Oncology
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Objective:1.Immunohistochemistry(IHC)technique was used to detect the expression of PD-L1 in nasopharyngeal carcinoma(NPC),and to explore the correlation between its high expression and clinical parameters.2.To analyze the correlation between the PD-L1 expression and 18F-FDG PET/CT parameter SUVmax in NPC.To investigate the possibility of assessing PD-L1 expression using 18F-FDG PET/CT.3.To study the relationship between LMP1 and PD-L1 expression in NP69 cells,and to explore the possible mechanism of high PD-L1 expression in NPC.Methods:A total of 102 patients with NPC diagnosed by biopsy at the First Affiliated Hospital of Xiamen University from December 2017 to September 2018 were enrolled.IHC technique was used to detect the expression of PD-L1 on tumor cells(PD-L1TC)and on immune cells(PD-L1IC).Spearman rank correlation test was used to analyze the correlation of PD-L1 with clinical parameters.Of the 102 patients,36 of them underwent PET/CT,and the SUVmax value of the primary tumor(SUVmax_T)and metastatic lymph node(SUVmax_N)were calculated.The correlation between PD-L1 expression and SUVmax was analyzed by Spearman test.When evaluating PD-L1 expression,the Cut-off value of SUVmax was determined using the ROC curve.Real-time PCR was used to detect the mRNA expression levels of LMP1 and PD-L1 in 17 NPC tissues and 15 normal nasopharyngeal tissues,and significant differences were analyzed by independent sample t-test.After overexpression of LMP1 in the NP69 eell line,the transcription and translational levels of PD-L1 were detected by Real-time PCR and Western-blotting.Results:1.Only one of 102 patients with NPC had negative PD-L1TC expression(<1%),and all patients(100%)had positive PD-L1IC expression(?%).The expression of PD-L1TC was positively correlated with T stage,while the expression of PD-L1IC was negatively correlated with plasma EBV-DNA load,N staging,M staging and TNM staging.2.Both SUVmax T and SUVmax N were positively correlated with PD-L1TC expression.When PD-L1TC was evaluated,the Cut-off values of SUVmax T and SUVmax_N were 8.83 and 5.60,respectively.3.The mRNA expressions of LMP1 and PD-L1 in NPC were significantly higher than those in normal nasopharyngeal tissues.LMP1 could promote the transcription and translation of PD-L1 in NP69 cells.Conclusions:1.High expression of PD-L1 is common in NPC,and the PD-L1 expression is correlated with clinical parameters.Therefore,it is necessary to further increase the sample size and eonduct long-term follow-up to further study its significance in clinical prognosis.2.The PD-L1TC expression in NPC is positively correlated with 18F-FDG-PET/CT parameter SUVmax value.The SUVmax may be used to evaluate the PD-L1TC expression in NPC.3.LMP1 can promote the expression of PD-L1 in NPC,which may be an important reason for the high expression of PD-L1 in NPC.
Keywords/Search Tags:Nasopharyngeal Carcinoma(NPC), PD-L1, LMP1, SUVmax
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