| Objective:Aspartyl beta-hydroxylase(ASPH)is highly expressed in a variety of cancers,but there are few studies on lung cancer.This study uses bioinformatics technology to conduct data mining and analysis in multiple tumor information databases and uses immunohistochemical(IHC)staining of independent samples to explore the expression,clinical significance,prognosis and possible molecular mechanisms of ASPH in non-small cell lung cancer(NSCLC),and summarized the potential of ASPH as a biomarker of NSCLC,so as to lay the foundation for subsequent research.Methods:Preliminary study on the expression of ASPH in NSCLC tissues in Oncomine and GEPIA databases.The RNA expression profiles and clinical data of 495 patients with lung adenocarcinoma(LUAD)and 400 patients with lung squamous cell carcinoma(LUSC)were extracted from the TCGA database.After data mining and sorting,the expression differences of ASPH in tumor and normal tissues were further analyzed,and its clinical significance was estimated according to the correlation with clinicopathological parameters.In addition,from September 2019 to August 2020,107 cases of LUAD and 66 cases of LUSC tissues,paired adjacent tissues and corresponding clinical information in Department of thoracic surgery of Guizhou Provincial People’s hospital were selected as the research objects,and IHC was performed to verify the expression of ASPH in NSCLC.Kaplan-Meier plotter and GEPIA database were used to explore the relationship between ASPH expression and the survival time of LUAD and LUSC patients,and the survival information of patients in the Oncomine database was extracted and analyzed,and survival curves were drawn to verify the relationship between ASPH expression and patient prognosis.For the molecular mechanism involved in ASPH,we used the SRTING database to find the top 10 genes most closely related to ASPH,and used GO gene function annotation and KEGG signaling pathway enrichment analysis to explore possible biological processes and molecular functions.Gene Set Enrichment Analysis(GSEA)of ASPH gene further explores the signal pathway involved in NSCLC.Results:The five LUAD data sets and one LUSC data set from the Oncomine database all support the significant high expression of ASPH in tumor tissues(p<0.05).In the GEPIA database,the expression of ASPH is elevated in a variety of malignant tumors including LUAD and LUSC.In the TCGA cohort,the expression of ASPH was significantly different from the gender,smoking history,T stage,N stage,and M stage of LUAD and LUSC patients(p<0.001).Subsequently,independent sample immunohistochemistry in our hospital further confirmed that the expression level of ASPH was significantly higher in LUAD and LUSC tissues.The expression level of ASPH was significantly related to the age,tumor size,and TNM stage of LUAD patients(P<0.05),but has no statistical significance with the clinicopathological parameters of LUSC patients.In addition,in the three study cohorts including GEPIA,Kaplan-Meier plotter and Oncomine,high expression of ASPH was significantly associated with poor prognosis of patients with LUAD(p<0.05).However,in LUSC,high expression of ASPH was significantly associated with shorter overall survival(OS)only in Kaplan Meier plotter(p<0.05).Functional annotation analysis showed that ASPH and its related genes are mainly involved in calcium regulation,lung development,and hypoxia regulation.The KEGG signaling pathway is mainly enriched in the three pathways of FoxO,Notch and mTOR.Subsequently,GSEA was performed on the ASPH high expression samples from TCGA database LUAD and LUSC patients,respectively,and it was shown that in LUAD,MYC targets,interferon y response,TNF-α signaling via NFKB and E2F targets were the most significantly enriched top 4 signaling pathways;In LUSC,MTORC1 signaling,reactive oxygen species pathway,protein secretion and androgen response are the top 4 signaling pathways that are most significantly enriched.Conclusion:The expression level of ASPH in LUAD and LUSC is significantly higher than that in adjacent tissues,which is obviously related to multiple clinicopathological parameters.The high expression of ASPH is significantly related to the poor prognosis of LUAD patients,and its prognostic value in LUSC still needs further study.ASPH participates in a number of key cancer-related signaling pathways and regulates a variety of biological processes.The pathogenic mechanisms in LUAD and LUSC are likely to be different,which requires further in vivo and in vitro experiments to verify.In summary,ASPH may be a cancer-promoting factor and potential prognostic biomarker of NSCLC.These studies provide a theoretical basis for the pathogenesis of NSCLC and anti-tumor targeted therapy. |
PDF Full Text Request