Prognostic Gene Expression, Stemness and Immune Microenvironment in Pediatric Tumors

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Pediatric tumors often originate from embryonal cells with stem cell-like morphology.
• Recent research links tumor
• stemness
• to a diminished immune response.

Purpose of the Study:

• To systematically investigate the relationship between prognostic gene expression, stemness, and the immune microenvironment in pediatric and young adult tumors.
• To explore how stemness scores (mRNAsi) correlate with clinical and morphologic subtypes and patient outcomes.

Main Methods:

• Analysis of transcriptomes from 4068 pediatric and young adult tumors.
• Utilized prognostic gene expression (PRECOG) and immune cell infiltration (CIBERSORT) analysis.
• Validated findings in Wilms tumor tissue (n=78).

Main Results:

• Stemness scores (mRNAsi) correlate with specific subtypes in Wilms tumors, neuroblastomas, synovial sarcomas, atypical teratoid rhabdoid tumors, and germ cell tumors.
• High mRNAsi is linked to shorter survival in neuroblastomas.
• In Wilms tumors, high mRNAsi correlates with blastemal morphology and fewer M2 macrophages, while differentiated areas show higher M2 macrophage infiltration.

Conclusions:

• Distinct patterns of gene expression and immune microenvironment exist across pediatric tumor entities.
• Stemness influences the immune landscape, with specific associations observed in Wilms tumors and neuroblastomas.
• Local microanatomy may regulate immune responses within tumors, as suggested by M2 macrophage distribution in Wilms tumors.