| Background and purpose: Malignant mesothelioma(MM)is a rare and highly aggressive cancer for which there are limited treatment options available.Most patients are diagnosed at an advanced stage,with a median survival time of 9-12 months and a 5-year survival rate of less than 10%,and patients with non-epithelial-like tissue types of MM have a poor prognosis.Although MM is still a rare tumor,the incidence of MM is quietly increasing with the rapid development of global industrialization and the widespread use of asbestos products.Therefore,it is important to study the genes that regulate the pathogenesis of MPM for the diagnosis and treatment of MPM.Lysyl oxidase(LOX)is a class of copper-dependent amine oxidases whose activity is active in the cross-linking of collagen and elastin.l OX proteins have a role in catalyzing the cross-linking of the extracellular matrix(ECM),primarily to maintain the structure and function of the ECM.Previous studies have shown that the LOX family promotes tumor progression mainly by promoting collagen cross-linking,promoting EMT,activating the FAK/Src pathway and promoting the formation of the pre-metastatic microenvironment.aberrant expression of LOX genes is closely associated with the development of many types of malignancies and plays an important role in promoting tumor metastasis in particular.However,the expression of LOX genes in MPM and the mechanism of their role in the development of MPM is not clear.Therefore,this study focuses on the mechanism of the role played by LOX in the development of MPM and provides a potential molecular target for subsequent early diagnosis and prognostic assessment.Methods: The correlation between LOX gene expression levels in MPM,tumor clinicopathological parameters and prognosis was analyzed using public tumor databases.The relationship between LOX expression in MPM and immune infiltrating cells was analyzed by TIMER platform.In addition,40 paraffin section samples and 5 fresh surgical samples from Dajao County,Chuxiong Prefecture,a high MPM prevalence area,were collected in this study to investigate the expression of LOX gene and LOX protein in MPM tissues by q PCR,immunohistochemistry and Western Blotting.Normal pleural cells and MPM cells were cultured in vitro,and the expression of LOX gene and protein were analyzed by q PCR and Western Blotting to investigate the effect of BAPN on the proliferation and migration of MPM cells by inhibiting MPM cells using BAPN,a small molecule inhibitor of LOX.Results: Analysis of public databases revealed that LOX gene was highly expressed in MPM.n-stage samples,t-stage samples and tumor types in MPM clinical samples correlated with LOX expression.high LOX expression predicted poor overall survival(OS,Overall Survival)and disease-free survival(DFS,Disease Free)in MPM patients.Survival).The patient’s tumor type and the expression of LOX are risk factors affecting the prognosis of MPM patients.It was found that CALB2 and MLSN were negatively correlated with LOX expression and THBS2 was positively correlated with LOX expression in MPM;LOXL2 and LOXL4 gene expression were positively correlated with LOX gene expression.q PCR,immunohistochemistry and Western Blotting results showed that LOX gene was highly expressed in MPM tissues and cells.Western Blotting results in cultured tumor cells showed that BAPN could significantly inhibit LOX gene expression.CCK-8 and scratch assays showed that the proliferation and migration of MPM cells were significantly inhibited in the presence of BAPN,a small molecule inhibitor of LOX.Conclusion: LOX is highly expressed in MPM cells and tissues,and BAPN,a small molecule inhibitor of LOX,can effectively inhibit the proliferation and migration of MPM cells.high LOX gene expression is associated with poor prognosis in MPM patients and is expected to be a potential marker for MPM diagnosis. |
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