Bioinformatics Analysis Of Surfactant Protein A1 And Its Preliminary Exploration In Immune Microenvironment Of Lung Cancer

Background:With the ongoing development of sequencing technology,genome instability and mutation became an important hallmark of both human genetic disease and cancer.A better understanding of the molecular mechanism of oncogenesis urgently needed,so as to provide more targets for accurate treatment of lung cancer and even cancer.Pulmonary surfactant protein A1(SFTPA1)plays a critical role in maintaining lung tissue homeostasis and its disruption could cause lung diseases and even lung cancer.Notablely,previous work found that SFTPA1 is a potential biomarker for lung cancer,but the mechanism remians unclear.As a regulator of innate immunity in lung tissues,SFTPA1 has been rarely studied in the immune microenvironment of lung cancer.Aiming at this problem,we explored the expression profile of SFTPA1 in various organs and tissues,the prognostic value and function of SFTPA1 in multiple tumors and the role of SFTPA1 in the immune microenvironment of lung cancer.Methods:Our study explored the expression profile of SFTPA1 in GTEx,TCGA and Oncomine database,and future validated in our samples of BALB/c mice,human normal tissues and human tumor tissues by immunohistochemistry assay.The prognostic values were evaluated by Kaplan-Meier Plotter Database Analysis.Principal components analysis and pathway enrichment analyses were exerted to identify the functional heterogeneity of SFTPA1 in various tumors.ESTIMATE,TIMER,and CIBERSORT databases were employed to analyze the correlation between SFTPA1 and tumor-infiltrating immune cells in lung cancer.The transcriptional regulation network was constructed based on differentially expressed transcription factors and microRNAs from the cancer genome atlas(TCGA)database.Results:1.The SFTPA1 widely expressed in various organs and tissues of BALB/c mice,human normal tissues and various types of human tumor tissues,and mostly expressed in lung and lung cancer tissues.Moreover,we observed differential expression of SFTPA1 mRNA in several type of tumor tissues and their matched normal tissues,and was less expressed in lung adenocarcinoma and lung squamous cell carcinoma than in normal lung tissues.2.The lower level expression of SFTPA1 was significantly associated with longer overall survival(OS)in nine different type cancers including lung squamous cell carcinoma(LUSC),and the higher level was significantly associated with longer OS in 5 different type cancers including liver Lung adenocarcinoma(LUAD).3.The expression level of SFTPA1 mRNA was positively correlated with the immune microenvironment,and positively correlated with the infiltration level of tumor-related macrophages.There were fewer activated CD4+memory cells and M1 macrophages in the group with high SFTPA1 expression in LUAD.There were higher B memory cells,monocytes,dendritic cells and mast cells,and fewer M2 macrophages and NK cells in the group with high SFTPA1 expression in LUSC.4.The has-miR-3200-3p inhibits the expression of SFTPA1 mRNA and the transcription factor FOXA2 promotes it in LUSC.Conclusions:1.The expression of SFTPA1 in LUAD and LUSC was lower than that in normal lung tissue.The patients with high expression of SFTPA1 in LUAD were associated with good prognosis,while those with high expression of SFTPA1 in LUSC were associated with poor prognosis,which has certain research value.2.In LUAD and LUSC,SFTPA1 could affect the changes of immune microenvironment of lung cancer,especially related to tumor-associated macrophages.has-miR-3200-3p and FOXA2 might be potential transcriptional regulators of SFTPA1 in lung squamous cell carcinoma.