Expression Of NUT,BRD4 And SOX2 In Poorly Differentiatedlung Cancer And Analysis Of Clinicopathological Features

Background:Tumor molecular markers play an increasingly important role in the diagnosis,treatment and prognosis of tumors.Searching for meaningful markers has become a hot topic in tumor research and clinical research,and has made important progress.NUT(nuclear protein in testis)is a relatively specific marker found in poorly differentiated cancers in the midline of the diaphragm,such as the lung and mediastinum.At present,there are few studies on NUT at home and abroad,mainly concentrated on In the study of NUT cancer in the mediastinum,thymus,head and neck,NUT cancer was also found in areas other than the midline,such as the lungs and bladder.In addition to NUT cancer,the presence or absence of NUT in other cancers has not been reported.Although NUT is reported in the lung,the expression characteristics,clinicopathological features,and related gene regulation mechanisms of NUT in poorly differentiated lung cancer have not been reported.There are few studies on the mechanism of action of NUT in tumorigenesis and development.At present,a few foreign cytological studies have found that BRD4-NUT fusion oncogenes cause abnormal activation of SOX2 and drive stem cell proliferation of NMCs(nuclear protein in testis midline carcinoma).And cell transformation.BRD4-NUT-induced abnormal SOX2 activation was observed in multiple NMC cell lines as well as in NMC primary tumors,but studies in poorly differentiated lung cancer have not been found.This study is based on the analysis of large sample sizes of poorly differentiated lung cancer-related immunophenotypic changes and molecular genetic changes to explore the expression of NUT,BRD4,SOX2 in poorly differentiated lung cancer,between BRD4,SOX2 and NUT proteins.Relationship and preliminary study on the expression of BRD4-NUT fusion gene in poorly differentiated lung cancer and the relationship between these indicators and clinicopathological features,etc.,to explore possible molecular regulatory mechanisms,and to provide a prognostic assessment of tumors and to find potential therapeutic targets.The First Part Expression and analysis of NUT in poorly differentiated lung cancerPurpose:The expression of NUT in poorly differentiated lung cancer tissues was examined.The relationship between NUT expression and clinicopathological features of poorly differentiated lung cancer patients and its prognostic value were analyzed.The expression of BRD4-NUT fusion gene was also studied.Method:A retrospective analysis of 233 patients diagnosed with poorly differentiated lung cancer,and patients who had not previously received relevant treatment,collected relevant clinical data and conducted regular follow-up.All 233 cases of poorly differentiated lung cancer were further confirmed by pathological data or additional immunological markers,including 141 cases of poorly differentiated lung squamous cell carcinoma,82 cases of poorly differentiated lung adenocarcinoma,and 3 cases of poorly differentiated lung adenosquamous carcinoma.,7 cases of poorly differentiated small cell lung cancer.The expression of NUT in 233 cases of poorly differentiated lung cancer tissues andadjacent normal lung tissues was detected by immunohistochemical Elivision method.The data were analyzed using SPSS 23.0 software,and P < 0.05 was statistically significant.Results:1.In 141 cases of poorly differentiated lung squamous cell carcinoma,NUT was positively expressed in 11 cases(7.80%,11/141),of which 2 cases were strongly expressed;in 82 cases of poorly differentiated lung adenocarcinoma,NUT was positive in 19 cases(23.17%),19/82),in which 1 case was strongly expressed,and no expression was found in the other two groups.The positive expression rate of NUT was 13.45%(30/223).2.The expression of NUT was positively correlated with lymph node metastasis(LNM)in patients with poorly differentiated lung cancer,and negatively correlated with overall survival(OS).3.30 cases of NUT antibody positive expression,3 cases of strong expression of NUT and selected immunohistochemical marker semi-quantitative score of 4 NUT moderateintensity poorly differentiated squamous cell carcinoma and adenocarcinoma a total of 5cases,FISH detection 2 The BRD4-NUT fusion gene was present in 1 case of poorly differentiated lung squamous cell carcinoma with semi-quantitative score of 4 points and1 case of poorly differentiated adenocarcinoma with strong expression.Conclusions:1.NUT expression was found in poorly differentiated lung squamous cell carcinoma and poorly differentiated lung adenocarcinoma,but small cell lung cancer and poorly differentiated lung adenosquamous carcinoma were not expressed,and the reason for fewer cases was not excluded.Moreover,NUT may be an indicator of clinical pathology with poor prognosis in poorly differentiated lung cancer.2.The expression mechanism of NUT in poorly differentiated lung cancer may be related to the BRD4-NUT fusion gene.3.In poorly differentiated lung cancer,primary lung NUT cancer is rare.The Second Part Study on the relationship between BRD4,SOX2and NUT and its research in poorly differentiated lung cancerPurpose:The expression of BRD4,SOX2 protein in poorly differentiated lung cancer was detected and its relationship with clinicopathological features and prognostic value were analyzed.The relationship between BRD4,SOX2 protein and NUT was analyzed.Method:Thirty cases of poorly differentiated lung cancer with positive NUT expression were selected from the total cases,and 30 cases of poorly differentiated lung cancer with negative NUT expression were selected as the control group.The expression of BRD4 and SOX2 in 60 cases of poorly differentiated lung cancer were detected by immunohistochemical Elivision method.The data were analyzed using SPSS 23.0software,and P < 0.05 was statistically significant.Results:1.The positive expression of BRD4 in 30 cases of NUT positive expression group and negative expression group were 25 cases and 16 cases respectively,and the positive expression of SOX2 was 18 cases and 10 cases respectively.2.The expression of BRD4 and SOX2 was positively correlated with lymph node metastasis(LNM)in patients with poorly differentiated lung cancer,and negatively correlated with overall survival(OS).3.NUT protein was positively correlated with the expression of BRD4 and SOX2 proteins.Conclusions:1.The expression of BRD4 and SOX2 in cancer tissues of poorly differentiated lung cancer patients is presumed to play an important role in tumorigenesis anddevelopment.2.The expression of NUT was positively correlated with the expression of BRD4 and SOX2 in poorly differentiated lung cancer.It is speculated that three factors may play an important role in tumorigenesis and development.