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ORIGINAL RESEARCH article

Front. Genet.
Sec. Computational Genomics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1431668
This article is part of the Research Topic The role of genes and network pharmacology in new drug discovery View all articles

Exploring the Molecular Landscape of Osteosarcoma through PTTG Family Genes Using a Detailed Multi-Level Methodology

Provisionally accepted
Yulin Lu Yulin Lu 1Danjun Wang Danjun Wang 1Guoao Chen Guoao Chen 1Zitong Shan Zitong Shan 1Dongmei Li Dongmei Li 2*
  • 1 School of Medicine, Shihezi University, Shihezi, China
  • 2 NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China

The final, formatted version of the article will be published soon.

    Background: Osteosarcoma (OS) poses a significant clinical challenge, necessitating a comprehensive exploration of its molecular underpinnings. Methods: This study explored the roles of PTTG family genes (PTTG1, PTTG2, and PTTG3P) in OS, employing a multifaceted approach encompassing molecular experiments, including OS cell lines culturing, RT-qPCR, bisulfite and Whole Exome Sequencing (WES) and in silico experiments, including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets-based validation, overall survival, gene enrichment, functional assays, and molecular docking analyses. Results: Our findings reveal a consistent up-regulation of PTTG genes in OS cell lines, supported by RT-qPCR experiments and corroborated across various publically available expression datasets databases. Importantly, ROC curve analyses highlight their potential as diagnostic markers. Moving beyond expression profiles, we unveil the epigenetic landscape by demonstrating significant hypomethylation of CpG islands associated with PTTG genes in OS. The negative correlation between methylation status and mRNA expression emphasizes the regulatory role of promoter methylation in PTTG gene expression. Contrary to expectations, genetic mutations in PTTG genes are rare in OS, with only benign mutations observed. Moreover, functional assays also confirmed the oncogenic roles of the PTTG gene in the development of OS. Lastly, we also revealed that Calcitriol is the most appropriate drug that can be utilized to treat OS in the context of PTTG genes. Conclusion: The identification of PTTG genes as potential diagnostic markers and their association with epigenetic alterations opens new avenues for understanding OS pathogenesis and developing targeted therapies. As we navigate the complex landscape of OS, this study contributes essential insights that may pave the way for improved diagnostic and therapeutic strategies in its management.

    Keywords: Osteosarcoma, PTTG family genes, biomarker, prognosis, Molecular landscape

    Received: 12 May 2024; Accepted: 10 Jul 2024.

    Copyright: © 2024 Lu, Wang, Chen, Shan and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Dongmei Li, NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.