| Objective:The mortality rate of lung cancer accounts for all diagnosed malignant tumors has always been ranked first.Among them,the treatment of squamous cell lung carcinoma(SqCLC)has faced with huge challenges.Therefore,it is of great theoretical and clinical significance to find more specific molecular targets or biomarkers in squamous cell lung carcinoma.Platelet-derived growth factor receptors(PDGFR),including PDGFR-a and PDGFR-β,it is an important cell signal transduction pathway receptor[1-2],the PDGF/PDGFR signaling pathway can regulate a variety of biological processes,including cell growth,cell differentiation,cell migration,and angiogenesis[3].PDGFRB gene is highly expressed in a variety of tumors such as hematological tumors,glioma,liver cancer,prostate cancer[4-8].Functional experiments have shown that PDGFRB is a proto-oncogene[9]Excavating public databases,we found that the high expression of PDGFRB gene in lung squamous cell carcinoma corresponds to a poor clinical prognosis(P=0.009,N=49),which suggests that the PDGFRB gene may be a biomarker related to the treatment or prognosis of squamous cell lung carcinoma.This project mainly use cell experiments to detect the role of mutated PDGFRB in signal transduction,and then use immunohistochemistry(IHC)to retrospectively analyze the expression and activation of PDGFRB in clinical samples of squamous cell lung carcinoma,and analysis of the relationship between high expression of PDGFRB protein and clinical prognosis.Methods:1.Explore the clinical therapeutic value of PDGFRB gene mutations through tissue sample detection and in vitro experiments.(1)Collect the data of squamous cell lung carcinoma patients in the First Affiliated Hospital of Kunming Medical University in the past 6 years.According to the case data,200 patients with squamous cell lung carcinoma diagnosed by pathological diagnosis are screened,clinical information of the patients are collected,and 200 patients are followed up.(2)Construct a PDGFRB overexpression cell line,and use Western Blot(WB)to detect the phosphorylation of downstream signaling pathway proteins,such as ERK.2.Detection of PDGFRB protein expression in pathological tissues of squamous cell lung carcinoma by IHC.3.Analyze the relationship between the expression level of PDGFRB gene and the pathological grade and stage.4.Analyze the relationship between PDGFRB gene expression and prognostic survival.5.Analyze the relationship between the prognosis of patients with squamous cell lung carcinoma and clinical related factors.6.The data was analyzed by SPSS26.0 software,P≤0.05 means that the difference is statistically significant.Results:1.According to the sequencing data of cell experiments,the human PDGFRB wild-type and mutant plasmids were constructed.Western blotting was used to detect phosphorylation of downstream signaling pathways.It was found that,compared with wild-type PDGFRB,mutant PDGFRB activates the MAPK-ERK pathway more strongly.2.The PDGFRB antibody(Y92)was used for IHC analysis,and the results showed that there were 169 cases(90%)of patients with no expression and low expression,and 19 cases(10%)of patients with high expression.3.The expression of PDGFRB gene in patients with squamous cell lung carcinoma has no correlation with the patient’s age,tumor differentiation,lymph node metastasis and TNM staging.4.IHC was used to detect the expression of phosphorylated PDGFRB gene in the pathological tissues of squamous cell lung carcinoma.The analysis results showed that there was no significant difference between the expression of this gene and the survival time of patients.5.There was statistical differences between the prognostic survival time of patients with squamous cell lung carcinoma and the tumor TNM stage,lymph node metastasis,and tumor cell pathological type.Conclusion:1.A mutant of PDGFRB activates the MAPK-ERK pathway.2.There was no statistical difference between the expression of PDGFRB gene in squamous cell lung carcinoma and the patient’s survival time. |
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