System analysis based on Anoikis-related genes identifies MAPK1 as a novel therapy target for osteosarcoma with

Zhouwei Wu1,2, Jiapei Yu1,2, Tao Han3,2

  • 1Department of Orthopedics, the Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.

PubMed
Abstract

Insights

We developed a new risk score model using Anoikis-related genes to predict osteosarcoma prognosis. This model aids clinicians and identifies MAPK1 as a potential therapeutic target for osteosarcoma treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genomics

Background:

  • Osteosarcoma (OS) is a prevalent pediatric bone cancer with a poor prognosis.
  • Anoikis, a mode of cell death, has unexplored roles in OS.

Purpose of the Study:

  • To investigate the role of Anoikis-related genes in osteosarcoma.
  • To develop a prognostic model for OS based on Anoikis-related genes.
  • To explore the relationship between these genes, the tumor microenvironment, and drug sensitivity.

Main Methods:

  • Differential gene expression analysis between metastatic and non-metastatic OS groups.
  • Machine learning algorithms (LASSO, SVM-RFE) for gene selection.
  • Cox regression for prognostic gene identification and risk score development.
  • Correlation analysis with tumor microenvironment and drug sensitivity data.

Main Results:

  • A novel prognostic model was developed using three Anoikis-related genes: MAPK1, MYC, and EDIL3.
  • The model demonstrated reliability in survival and ROC analyses.
  • Prognostic genes correlated with immune cell infiltration; aberrant expression of MAPK1 and MYC was observed in OS cells.
  • Nilotinib showed potential to induce OS cell apoptosis and downregulate MAPK1.

Conclusions:

  • A novel Anoikis-related risk score model can aid clinical prognosis assessment for osteosarcoma patients.
  • Tumor immune microenvironment and drug sensitivity analyses offer insights into OS mechanisms.
  • MAPK1 presents a potential therapeutic target for neoadjuvant chemotherapy in osteosarcoma.

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