An Interpretable Four-Gene Cell-Cycle Signature Links Malignant Progression to Adverse Survival in Adult Primary...

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Adult diffuse gliomas are heterogeneous and lethal.
• Current understanding of malignant progression and survival prediction needs improvement.

Purpose of the Study:

• To evaluate a compact transcriptomic program for summarizing glioma malignant progression.
• To assess the program's ability to predict adverse survival outcomes.

Main Methods:

• Analysis of adult primary gliomas (WHO grades II-IV) from CGGA cohorts (mRNAseq_693 and mRNAseq_325).
• Prioritization of four mitotic genes (CDK1, CCNB2, CDCA3, PTTG1) using a literature-informed framework.
• Evaluation of classifiers via cross-validation and assessment of a four-gene score using survival models.

Main Results:

• Identified 773 differentially expressed genes between WHO grade IV and lower-grade gliomas.
• The four-gene score demonstrated strong classification performance (AUROC ~0.79) in both primary and validation cohorts.
• The score correlated with tumor grade and predicted shorter survival, independent of age, grade, and IDH status.

Conclusions:

• The four-gene score effectively captures grade-associated proliferative biology in gliomas.
• This score provides reproducible survival risk prediction across independent cohorts.
• It serves as a valuable research biomarker for glioma biology and prognosis.