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巨噬细胞和单核细胞介导的氧化磷酸化激活与肾母细胞瘤的预后及临床治疗策略相关。

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

作者信息

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

机构信息

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.

Institute of Urology, Anhui Medical University, Hefei 230022, Anhui, China.

出版信息

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

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.

摘要

肾母细胞瘤是儿童恶性肿瘤的第四大主要病因,但肿瘤微环境与预后之间的详细关系仍 largely 不清楚。在本研究中,收集了来自TARGET和安徽医科大学第一附属医院的基因表达谱和临床信息。在比较相关免疫细胞的预后价值后,我们基于单核细胞浸润、巨噬细胞浸润、分期和性别建立了一个列线图来预测肾母细胞瘤的预后。进一步的结果表明,基质金属蛋白酶9与预后或巨噬细胞浸润之间的关系最为显著。同时,通过基因集富集或变异分析以及免疫组织化学染色,我们证明高度富集的枢纽基因与激活的氧化磷酸化途径密切相关。最后,通过肿瘤免疫功能障碍和排除算法,揭示了我们的列线图在预测临床治疗反应方面具有令人满意的判别性能。抗PD1治疗更适合列线图得分高的肾母细胞瘤患者,而化疗对列线图得分低的患者更有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ceb/9271979/c49661e0fffe/ga1.jpg

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