Clinical Prognostic Factors and Integrated Multi-Omics Studies Identify Potential Novel Therapeutic Targets for Pediatric Desmoid Tumor

Abstract

Abstract Background Desmoid tumor (DT), also known as desmoid-type fibromatosis (DTF) or aggressive fibromatosis (AF) is a rare mesenchymal tumor affecting both children and adults. It is non-metastasis but infiltrative, growing with a high recurrence rate to even cause serious health problems. This study investigates the biology of desmoid tumors through integrated multi-omics studies. Methods We systematically investigated the clinical data of 98 extra-abdominal cases in our pediatric institute and identified some critical clinical prognostic factors. Moreover, our integrated multi-omics studies (Whole Exome Sequencing, RNA sequencing, and untargeted metabolomics profiling) in the paired PDT tumor/matched normal tissues identified more novel mutations, and potential prognostic markers and therapeutic targets for PDTs. Results The top mutation genes, such as CTNNB1 (p.T41A and p.S45F) and MUC4 (p.T3775T, p.S3450S, etc.), were observed with a mutation in more than 40% of PDT patients. We also identified a panel of genes that are classed as the FDA-approved drug targets or Wnt/β-catenin signaling pathway-related genes. The integrated analysis identified pathways and key genes/metabolites that may be important for developing potential treatment of PDTs. We also successfully established six primary PDT cell lines for future studies. Conclusions These studies may promote the development of novel drugs and therapeutic strategies for PDTs.

Keywords

• Clinical prognostic factors
• Whole exome sequencing
• RNA sequencing
• Untargeted metabolomics profiling
• Pediatric desmoid tumor