{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T17:03:39Z","timestamp":1784653419769,"version":"3.55.0"},"reference-count":22,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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\u2013IV gliomas from the CGGA mRNAseq_693 cohort and used CGGA mRNAseq_325 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\u2013Meier 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 \u00b1 0.048 (95% CI 0.784\u20130.802), with average precision of 0.701 \u00b1 0.063. In the independent CGGA mRNAseq_325 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 \u22120.153. 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\u20131.49; p = 0.002) and in the independent cohort (n = 217; HR = 1.58, 95% CI 1.25\u20132.00; p &lt; 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.<\/jats:p>","DOI":"10.3390\/genes17070833","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T16:16:39Z","timestamp":1784650599000},"page":"833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Interpretable Four-Gene Cell-Cycle Signature Links Malignant Progression to Adverse Survival in Adult Primary Diffuse Glioma: A CGGA Transcriptome Study"],"prefix":"10.3390","volume":"17","author":[{"given":"Hongkai","family":"Jia","sequence":"first","affiliation":[{"name":"Renal Division, Peking University Institute of Nephrology, Peking University First Hospital & Key Laboratory of Renal Disease, Ministry of Health of China & Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China & Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences & Beijing Key Laboratory of Precision Medicine and New-Drug\/Equipment Development for Severe Kidney Disease, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Pu","sequence":"additional","affiliation":[{"name":"College of Bioengineering, Beijing Polytechnic University, Beijing 100176, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Ultrasound Medicine, People\u2019s Hospital of Yubei District, Chongqing 401120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro-Oncology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. 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