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

IF 3.7 3区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

Biological Procedures Online Pub Date : 2022-12-20 DOI:10.1186/s12575-022-00180-0

Bo Ning, Peng Huang, Lining Zhu, Zhijie Ma, Xiaoli Chen, Haojun Xu, Ruixue Ma, Chengyun Yao, Pengfei Zheng, Tian Xia, Hongping Xia

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引用次数: 1

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.

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临床预后因素和综合多组学研究确定了儿童硬纤维瘤潜在的新治疗靶点。

背景:纤维瘤(Desmoid tumor, DT)，又称纤维瘤型纤维瘤病(Desmoid -type fibromatosis, DTF)或侵袭性纤维瘤病(aggressive fibromatosis, AF)，是一种罕见的儿童和成人间充质肿瘤。它是非转移性的，但具有浸润性，生长且复发率高，甚至引起严重的健康问题。本研究通过综合多组学研究探讨硬纤维瘤的生物学特性。方法:系统分析我院98例腹外疝患者的临床资料，找出影响预后的关键因素。此外，我们在配对的PDT肿瘤/匹配的正常组织中进行的综合多组学研究(全外显子组测序、RNA测序和非靶向代谢组学分析)发现了更多新的突变、潜在的PDT预后标志物和治疗靶点。结果:CTNNB1 (p.T41A、p.S45F)和MUC4 (p.T3775T、p.S3450S等)等顶级突变基因在超过40%的PDT患者中出现突变。我们还确定了一组被归类为fda批准的药物靶标或Wnt/β-catenin信号通路相关基因的基因。综合分析确定了可能对开发潜在治疗pdt很重要的途径和关键基因/代谢物。我们还成功建立了6个PDT原代细胞系，用于未来的研究。结论:这些研究可能促进pdt新药和治疗策略的开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biological Procedures Online 生物-生化研究方法

CiteScore

10.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： iological Procedures Online publishes articles that improve access to techniques and methods in the medical and biological sciences. We are also interested in short but important research discoveries, such as new animal disease models. Topics of interest include, but are not limited to: Reports of new research techniques and applications of existing techniques Technical analyses of research techniques and published reports Validity analyses of research methods and approaches to judging the validity of research reports Application of common research methods Reviews of existing techniques Novel/important product information Biological Procedures Online places emphasis on multidisciplinary approaches that integrate methodologies from medicine, biology, chemistry, imaging, engineering, bioinformatics, computer science, and systems analysis.