Exploration of biological significance of m6A-related genes in Wilms tumor

Abstract Background: Wilms tumor (WT) is an embryonal abdominal malignant tumor which is a common renal malignant tumor in children. N6-methyladenosine (m6A) RNA methylation can dynamically regulate the development of tumors. However, m6A-related genes in WT have not yet been identified and researched. Methods: In this study, the RNA-seq data of TARGET-WT were extracted from the UCSC Xena for bioinformatics analysis. Results: 296 candidate hub genes were obtained by intersecting 3 gene sets (8610 gene modules with significantly associated m6A RNA methylation score, 7774 differentially expressed genes (DEGs) between 121 WT patients and 6 control samples, 763 DEGs between high and low score groups of m6A RNA methylation). Survival analysis of the 296 genes yielded 4 hub genes (ADGRG2, CPD, CTHRC1, and LRTM2) associated with WT prognosis. Subsequently, a prediction model with the 4 hub genes was developed and the model had good predictive power for the WT prognosis. In addition, 7 immune gene sets were obtained by intersecting 2 gene sets (18 significant difference immune gene sets between the WT group and control group, 10 immune gene sets related to the hub genes). Among them, APC_co_stimulation, CCR, Macrophages, Parainflammation, Treg, and Type_II_IFN_Reponse were low expressed in the WT, and only Th1_cells were highly expressed in the WT. APC_co_stimulation, CCR, Macrophages, Parainflammation, Treg, and Type_II_IFN_Reponse are negatively correlated with LRTM2, Th1_cells are positively correlated with ADGRG2, CCR is negatively correlated with CPD, CCR is positively correlated with CTHRC1. Finally, qRT-PCR results showed that the expression levels of the 4 hub genes were up-regulated in different WT cell lines compared with 293T cell lines. Conclusion: In conclusion, ADGRG2, CPD, CTHRC1, and LRTM2 may be m6A-related genes in WT, which have potential prognostic value and play an immunoregulation role in WT.