Expression Characteristics and Biological Functional Role of FLG in Gastric Cancer

Abstract

Abstract Background Filaggrin gene (FLG) plays a fundamental role and is associated with tumor malignant progression and maybe used as a new diagnostic biomarker for many cancers. Nevertheless, the characteristics and biological function in Gastric Cancer (GC) have not yet been elucidated. Thus, we focus on FLG expression, the association with immune infiltration and biological functions in GC. Methods The TCGA and GTEx databases were used to identify the mRNA expression of FLG in GC. We used the HPA database to identify the protein expression of FLG in GC. The Cox regression, Kaplan-Meier and nomogram prediction model were used to analysis the relationship between FLG and survival. We also used the logistic regression to analyze the relationship between FLG expressions and pathological features. FLG genetic modification information was derived from the cBioPortal and the GSCALite database. The relationship between FLG expression and microsatellite instability (MSI), DNA methyltransferases, immune-related genes, tumor mutational burden (TMB) were analyzed. The ESTIMATE and other two methods were evaluated the association between FLG expression and the immune infiltrating cells. The protein-protein interactions between Interacting Genes/ proteins (STRING) were established using the Search Tool. The FLG pathways were analyzed using GO and KEGG enrichment analyses. The ceRNA networks were identified in TCGA database. We performed differential expression of FLG and explored the biological role in tumor malignant progression of GC cells. Results We demonstrated that FLG is up-regulated in GC cells and significantly related with worse prognosis. Genetic alterations may lead to abnormal expression of FLG. Meanwhile, the expression of FLG was strongly correlated with immune characteristics. Moreover, FLG has many molecular functions and participates in many signaling pathways. In the cytology experiments, we found that silencing FLG expression largely inhibits GC cell metastasis via epithelial-mesenchymal transition (EMT) signaling pathway. Conclusion FLG is a novel and useful biomarker for prognosis, immune infiltration and malignant progression of GC.