Background: Adult diffuse gliomas are biologically heterogeneous and clinically lethal. We evaluated whether a compact transcriptomic program could summarize malignant progression and adverse survival. Methods: We analyzed adult primary WHO grades II–IV gliomas from the CGGA mRNAseq₆93 cohort and used CGGA mRNAseq₃25 as an independent validation cohort. CDK1, CCNB2, CDCA3, and PTTG1 were prioritized through a transparent, literature-informed mitotic-gene framework. Four classifiers were evaluated by five-fold cross-validation repeated 20 times, with all preprocessing restricted to each training fold. A training-defined four-gene score was assessed by Kaplan–Meier and Cox models. Results: The primary cohort contained 415 tumors, including 396 with evaluable survival. We identified 773 differentially expressed genes between WHO grade IV and WHO grades II/III tumors, and all four candidate genes increased monotonically with grade. In repeated cross-validation, the SVM achieved the highest mean AUROC of 0. 793 ± 0. 048 (95% CI 0. 784–0. 802), with average precision of 0. 701 ± 0. 063. In the independent CGGA mRNAseq₃25 cohort (n = 226), logistic regression achieved an AUROC of 0. 792. The four-gene score and a broader four-marker proliferation index showed similar discrimination, supporting the interpretation of the signature as a compact proliferation-axis proxy. The training-set median cut-off was −0. 153. The score remained associated with shorter survival after adjustment for age, grade, and IDH status in the primary cohort (n = 359; HR = 1. 28, 95% CI 1. 10–1. 49; p = 0. 002) and in the independent cohort (n = 217; HR = 1. 58, 95% CI 1. 25–2. 00; p < 0. 001). Conclusions: The four-gene score captures grade-associated proliferative biology and reproducible survival risk across two CGGA cohorts. It is a research biomarker rather than a standalone diagnostic or clinical decision tool.
Jia et al. (Tue,) studied this question.