HNRNPA2B1 as a potential therapeutic target for thymic epithelial tumor recurrence: An integrative network analysis

Thymic epithelial tumors (TETs) are rare malignant tumors, and the molecular mechanisms of both primary and recurrent TETs are poorly understood. Here we established comprehensive proteomic signatures of 15 tumors (5 recurrent and 10 non-recurrent) and 15 pair wised tumor adjacent normal tissues. We then proposed an inte-grative network approach for studying the proteomics data by constructing protein-protein interaction networks based on differentially expressed proteins and a machine learning-based score, followed by network modular analysis, functional enrichment annotation and shortest path inference analysis. Network modular analysis revealed that primary and recurrent TETs shared certain common molecular mechanisms, including a spliceo-some module consisting of RNA splicing and RNA processing, but the recurrent TET was specifically related to the ribosome pathway. Applying the shortest path inference to the collected seed gene module identified that the ribonucleoprotein hnRNPA2B1 probably serves as a potential target for recurrent TET therapy. The drug repo-sitioning combined molecular dynamics simulations suggested that the compound ergotamine could potentially act as a repurposing drug to treat recurrent TETs by targeting hnRNPA2B1. Our study demonstrates the value of integrative network analysis to understand proteotype robustness and its relationships with genotype, and provides hits for further research on cancer therapeutics.

Automated summary

In this study, the researchers constructed protein-protein interaction networks to investigate the molecular mechanisms of primary and recurrent thymic epithelial tumors (TETs). They found common molecular mechanisms shared by both types of tumors, as well as a specific pathway related to recurrent TETs. They also identified hnRNPA2B1 as a potential therapeutic target for recurrent TETs. Drug repurposing and molecular dynamics simulations suggested that ergotamine could be a potential repurposing drug for targeting hnRNPA2B1 in recurrent TETs. This study demonstrates the value of integrative network analysis in understanding proteotype robustness and its relationship with genotype, and provides leads for further research on cancer therapeutics.