A comprehensive analysis of the FOX family for predicting kidney renal clear cell carcinoma prognosis and the oncogenic role of FOXG1

Previous studies have confirmed that the forkhead box (FOX) superfamily of transcription factors regulates tumor progression and metastasis in multiple cancer. The purpose of this study was to develop a model based on FOX family genes for predicting kidney renal clear cell carcinom (KIRC) prognosis. We downloaded the transcriptional profiles and clinical data of KIRC patients from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. To build a new prognosis model, we screened prognosis-related FOX family genes using Lasso regression and Multivariate Cox regression analyses. Receiver operating characteristic (ROC) curves were used to evaluate model performance. Additionally, a prognostic nomogram was developed using clinical information and selected genes to improve the accuracy of prognostic prediction. We also investigated whether prognosis-related FOX family genes are related to the immune response in KIRC. Finally, we validated the oncogenic role of FOXG1 in KIRC using an in vitro tumor function assay. Six prognosis-related FOX family genes were screened: FOXO1, FOXM1, FOXK2, FOXG1, FOXA1, and FOXD1. The ROC curves indicated that our model was capable of making accurate predictions for 1-, 3-, and 5-year overall survival (OS). The nomogram further improved the accuracy of prognostic predictions. In addition, compared to those in patients with low-risk scores, high-risk scores predicted a decreased level of immune cell infiltration and a lower immune response rate. Moreover, the results of in vitro studies confirmed that FOXG1 supports the proliferation and invasion of KIRC.