Macrophages and monocytes mediated activation of oxidative phosphorylation implicated the prognosis and clinical therapeutic strategy of Wilms tumour

Abstract

Wilms tumour is the fourth leading cause of paediatric malignancy, but the detailed relationship between the tumour microenvironment and prognosis remains largely unclear. In this research, gene expression profile and clinical information from TARGET and the First Affiliated Hospital of Anhui Medical University were collected. After comparing the prognostic value of the associated immune cells, we established a nomogram to predict the prognosis of Wilms tumour based on monocyte infiltration, macrophage infiltration, stage, and sex. Further results showed that the most significant relationship between matrix metallopeptidase 9 and prognosis or macrophage infiltration. Meanwhile, by gene set enrichment or variation analyses and immunohistochemistry staining, we demonstrated that the most highly enriched hub genes were closely related to the activated oxidative phosphorylation pathway. Finally, through tumour immune dysfunction and an exclusion algorithm, the satisfactory discriminative performance of our nomogram was revealed for predicting the response to clinical therapy. Anti-PD1 therapy is more suitable for Wilms tumour patients with high nomogram points, and chemotherapies are more effective for patients with low nomogram score.