Site Editor
Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Tuesday, January 21, 2025
James W. Lillard Jr, PhD, MBA, of Morehouse School of Medicine, Atlanta, and colleagues revealed the importance of classifying high-grade serous ovarian cancer (HGSOC) based on mRNA subtypes to better understand its molecular and immune diversity, in an article in the Journal of Ovarian Research. This study identified four distinct mRNA subtypes—immunoreactive, differentiated, proliferative, and mesenchymal—each associated with unique gene-expression patterns and clinical traits. The findings highlight the immunoreactive subtype as particularly enriched with immune cell infiltration, including M1 and M2 macrophages and Th1 cells, suggesting it may be more amenable to immunotherapeutic strategies. Conversely, the mesenchymal and proliferative subtypes showed gene-expression signatures indicating tumor progression and cellular proliferation, suggesting alternative therapeutic targets.
“Our study reveals the complex interplay between mRNA subtypes and suggests genes contributing to molecular subtypes, underscoring the important clinical implications of mRNA subtyping in HGSOC,” the authors stated.
The investigators employed transcriptomic data and advanced computational methods to classify HGSOC into the four mRNA subtypes. Differential expression analysis and Weighted Gene Co-Expression Network Analysis (WGCNA) revealed key gene modules linked to clinical traits such as patient age, survival, and subtype classification. Gene Ontology analysis identified pathways involved in tumor progression and immune evasion, further clarifying the molecular underpinnings of HGSOC.
The immunoreactive subtype, driven by the M3 module, exhibited high immune cell infiltration, including macrophages (M1: P < .0001; M2: P < .01), Th1 cells (P < .01), and significant LAIR-1 expression (P = 1.63e-101). The M18 module associated with B cells demonstrated significant co-expression of FCRL5 and IRF4. Conversely, the mesenchymal subtype correlated with the M5 module and fibroblast infiltration (P < .0001), whereas the proliferative subtype was linked to the M15 module and ovarian stromal cells (P < .0001), underscoring subtype-specific therapeutic opportunities.
Disclosure: The study authors reported no conflicts of interest.
