Lack of <scp>WDFY4</scp> leads to impaired immune response and poor cancer prognosis

WDFY4 plays an essential role in the immune system by regulating B-cell growth and development and participating in antigen processing during cross-presentation. WDFY4 is closely related to asthma and systemic lupus erythematosus; however, its role in cancer remains unclear. The purpose of this study is to use bioinformatics to determine whether abnormal expression of WDFY4 is a risk factor for cancer and to preliminarily analyze the ways in which WDFY4 affects cancer through experiments. R language packages and bioinformatic database were used to mine the potential carcinogenic effect of WDFY4 and analyze the differential WDFY4 expression in cancer, gene mutations, different tumor prognoses, immune cell infiltration, tumor microenvironment, and DNA methylation correlation. H1975 and A549 cell lines were infected with lentiviruses to overexpress WDFY4, and the effect of WDFY4 on the activity, proliferation, apoptosis, and cell cycle of lung cancer cells was analyzed. WDFY4 was differentially expressed in human tumors in unpaired and paired samples. The differential expression of WDFY4 in unpaired and paired or protein samples from the Clinical Proteome Tumor Analysis Consortium of eight cancers was consistent. WDFY4 methylation was downregulated in 17 cancer types and caused prognostic differences in different directions in some cancers. WDFY4 overexpression significantly inhibited the activity and proliferation of lung cancer cell lines, promoted apoptosis, and caused cell cycle arrest. Differential WDFY4 expression in cancers leads to differences in the prognosis of various cancers. WDFY4 can be an independent prognostic factor for glioma, KIRC, and LUSC.