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Network Pharmacology, 2023, 8(1-2): 1-26
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Article

A further study on the topological structure of tumor signaling pathways

WenJun Zhang, XueBing Huang
School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China

Received 11 June 2021;Accepted 16 November 2021;Published online 6 September 2022;Published 1 June 2023
IAEES

Abstract
Tumorigenesis is a multifactor and multistep process, of which the change of metabolic signaling pathways plays a key role. Most of the previous studies on tumor signaling pathways focused mainly on the metabolic process and chemical processes of some selected metabolites, the tumorigenesis induced by abnormal signaling from mutation of this metabolite or gene, and the chemical structure of ligands, receptors and signaling proteins. However their network biology is seldom studied. Based on the previous studies, the present study was conducted to further analyze the topological structure of tumor signaling pathways using Pajek and UCINET software. Some critical metabolites were found and sensitivity analyses for signaling pathways were conducted. Centrality and core skeleton analysis showed that the crucial metabolites of AKT signaling pathway are Akt-p and Akt; the crucial metabolites of JAK-STAT signaling pathway are JAKs and 23(STATs-P)2; the crucial metabolites of p53 signaling pathway are p53-P-P, Gene Expression, Ac-p53 and (Ac-p53-P)2; the crucial metabolites of Ras signaling pathway are Ras-GTP, Ras-GDP and MEKK1; the crucial metabolites of TNF signaling-pathway are MEKIKs-P-NIK-P and TRADD, and for VEGF signaling pathway, the crucial metabolites are PIP3 and ANGIOGENESIS. The performance of cascade model was poor in predicting topological properties of tumor signaling pathways.

Keywords tumor;signaling pathway;betweenness centrality;closeness centrality;degree;cascade model.

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