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

Abstract

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 5year 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.

Integrative analysis of potential diagnostic markers and therapeutic targets for glomerulus-associated diabetic nephropathy based on cellular senescence

“…confirmed that FOXD1 may be dynamically regulated during kidney injury and repair in the developing mouse model ( 38 ). Previous studies established connections between FOXD1 and kidney tumor development, as well as mitochondrial metabolism ( 39 ). FOXD1 was additionally underscored to promote cell proliferation by targeting the sonic hedgehog pathway and cyclin-dependent kinase inhibitors ( 40 ).…”

Leveraging a disulfidptosis-based signature to improve the survival and drug sensitivity of bladder cancer patients

“…These assays were performed according to our previous studies ( 7 , 17 , 24 ). The primer sequences for qRT-PCR analysis were listed in Table S3 .…”

PLAGL2 promotes bladder cancer progression via RACGAP1/RhoA GTPase/YAP1 signaling

“…CCK-8 and colony formation assays were used to evaluate cell proliferation. For the CCK-8 assay, cells were seeded and cultured in 96-well plates for 48 h. The culture medium was replaced with CCK-8 solution, and the absorbance was measured at 450 nm after 4 h of incubation at 37 °C [ 22 ]. For the colony formation assay, cells were incubated in a 60-mm dish for two weeks and then fixed with paraformaldehyde for 20 min.…”

“…Wound-healing and transwell Matrigel invasion assays were employed to assess cell migration and invasion, respectively. Detailed procedures have been reported in our previous studies [ 3 , 22 ]. Briefly, for the wound-healing assay, a wound was made with a 200 µL pipette tip, and the wound areas were photographed every 3 h to record cell migration.…”