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

Jialin Meng; Yonghao Chen; Xiaofan Lu; Qintao Ge; Feixiang Yang; Suwen Bai; Chaozhao Liang; Juan Du

doi:10.1016/j.csbj.2022.06.052

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

Comput Struct Biotechnol J. 2022 Jun 27:20:3399-3408. doi: 10.1016/j.csbj.2022.06.052. eCollection 2022.

Authors

Jialin Meng^{1

2

3}, Yonghao Chen⁴, Xiaofan Lu^{5

6}, Qintao Ge^{1

2

3}, Feixiang Yang^{1

2

3}, Suwen Bai⁷, Chaozhao Liang^{1

2

3}, Juan Du⁷

Affiliations

¹ Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
² Institute of Urology, Anhui Medical University, Hefei 230022, Anhui, China.
³ Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei 230022, Anhui, China.
⁴ Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
⁵ State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
⁶ Department of Cancer and Functional Genomics, Institute of Genetics and Molecular and Cellular Biology, CNRS/INSERM/UNISTRA, Illkirch 67400, France.
⁷ The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, Guangdong, China.

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.

Keywords: Macrophages; Nomogram; Prognosis; Tumor-infiltrating immune cells; Wilms tumor.