PSIP1 Orchestrates Immune Escape in Osteosarcoma: Insights From Single-Cell Analysis and Implications for

Simin Liu1, Hong Yan1, Wei Ku1

  • 1Department of Spinal Surgery, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei, China.

Abstract

Insights

This study identifies PSIP1 as a key driver of immune escape in osteosarcoma (OS). High PSIP1 expression predicts poor immunotherapy response and survival, highlighting its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Osteosarcoma (OS) features a complex tumor microenvironment (TME) that often hinders immunotherapy effectiveness.
  • Identifying molecular mechanisms of immune escape (IE) is critical for enhancing treatment outcomes in OS.

Purpose of the Study:

  • To investigate the molecular drivers of immune escape in the OS tumor microenvironment.
  • To identify potential biomarkers for predicting immunotherapy response in osteosarcoma.

Main Methods:

  • Integrated single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic data.
  • Applied high-dimensional weighted gene coexpression network analysis (hdWGCNA) to identify IE-associated gene modules.
  • Utilized functional enrichment and Gene Set Enrichment Analysis (GSEA).

Main Results:

  • PSIP1 was identified as a significant prognostic hub gene within IE-related modules, predominantly expressed in malignant cells.
  • High PSIP1 expression correlated with reduced overall survival across multiple patient cohorts.
  • PSIP1 was linked to suppressed immune effector functions (B-cell signaling, lymphocyte chemotaxis, NK cell cytotoxicity) and predicted poor response to checkpoint blockade immunotherapy.

Conclusions:

  • PSIP1 is a novel orchestrator of immune evasion in osteosarcoma.
  • PSIP1 serves as a promising predictive biomarker for immunotherapy resistance in OS.
  • Targeting PSIP1 may offer a strategy to overcome therapeutic resistance in osteosarcoma.

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