Identification of the antitumor effects of Apigenin against tongue squamous cell carcinoma on the basis of experimental validation and bioinformatics analysis

Abstract

Background: Tongue squamous cell carcinoma (TSCC) is one of the most widespread cancers in oral cancer, but the current treatment outcome for TSCC is unsatisfactory. Apigenin has been shown to have antitumor effects in various tumors. However, the potential role of Apigenin (API) in TSCC has not been proven yet. Methods: The effects of API on the proliferation and migration ability of SCC-9 cells were measured by CCK8 assay and wound-healing assay. RNA-seq was executed to ensure differentially expressed genes (DEGs) in SCC-9 cells after API treatment. Then, combined with the gene expression data and relevant individual information of TSCC samples acquired from The Cancer Genome Atlas (TCGA), an API-related model was built through Lasso regression and multivariate Cox regression. Receiver operating characteristic (ROC) curve and a nomogram and calibration curve were created to forecast patient outcomes to improve the clinical suitability of the API-related signature. The relationships between the two risk groups and function enrichment, immune infiltration characteristics, and drug susceptibility were analyzed. Furthermore, RNA-seq was performed to verify the expression of API-related genes in SCC-9 cells. Results: We demonstrated that API could weaken the malignant behavior of SCC-9 cells and availably established the 7-API-related gene model to forecast the prognosis of TSCC patients, which was performed to divide TSCC patients into different risk groups, with risk scores working as an independent factor for participating TSCC related death. Besides, we confirmed that the model could be applied to assess prognostic status, tumor immune cell infiltration, and drug susceptibility. Moreover, TSCC cells treated with API, compared to the control group, have higher levels of TMEM213 and GPR158, and lower levels of CASP14 and ITGA5. Conclusions: Our research suggested the inhibition effect of API on TSCC cells and provided a substantial foundation for the next study into the links between API-related genes and related functions in TSCC patients.