{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:21:55Z","timestamp":1784805715452,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Gleason score (GS) is one of the best predictors of prostate cancer (PCa) aggressiveness; however, its biological features need to be elucidated. This study aimed to explore the biological characteristics of localized\/locally advanced PCa stratified using in silico GS analysis. Biological features were analyzed using gene set variation analysis and the xCell algorithm with mRNA expression in two independent public databases: The Cancer Genome Atlas (TCGA) (n = 493; radical prostatectomy cohort) and GSE116918 (n = 248; radiation therapy cohort). GS levels were positively correlated with the activity levels of cell proliferation-related gene sets, including E2F targets, the G2M checkpoint, the mitotic spindle, and MYC targets v1 and v2 in both cohorts. Furthermore, GS levels were positively associated with the activity levels of immune-related gene sets and infiltrating fractions of immune cells, including CD4+ memory T cells, dendritic cells, M1 macrophages, and Th2 cells, in both cohorts. Notably, GS levels were positively associated with the score levels of homologous recombination defects, intratumor heterogeneity, fraction genome alteration, neoantigens, and mutation rates in the TCGA cohort. In conclusion, PCa with high GS levels was associated with cancer cell proliferation, immune cell infiltration, and high mutation rates, which may reflect worse clinical outcomes.<\/jats:p>","DOI":"10.3390\/curroncol32070409","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T11:12:34Z","timestamp":1752837154000},"page":"409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unique Biological Characteristics of Patients with High Gleason Score and Localized\/Locally Advanced Prostate Cancer Using an In Silico Translational Approach"],"prefix":"10.3390","volume":"32","author":[{"given":"Shiori","family":"Miyachi","sequence":"first","affiliation":[{"name":"Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1404-1570","authenticated-orcid":false,"given":"Masanori","family":"Oshi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2458-5686","authenticated-orcid":false,"given":"Takeshi","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itaru","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7449-2015","authenticated-orcid":false,"given":"Kazuhide","family":"Makiyama","sequence":"additional","affiliation":[{"name":"Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004,  Kanagawa,  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu 514-8507, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.eururo.2022.11.023","article-title":"Disparities and Trends in Genitourinary Cancer Incidence and Mortality in the USA","volume":"84","author":"Schafer","year":"2023","journal-title":"Eur. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1007\/s10147-024-02575-3","article-title":"Urological cancer statistics on incidence from 1975 to 2019 and mortality from 1958 to 2022 in Japan","volume":"29","author":"Sasaki","year":"2024","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.eururo.2018.10.011","article-title":"Prognostic Value of Biochemical Recurrence Following Treatment with Curative Intent for Prostate Cancer: A Systematic Review","volume":"75","author":"Arfi","year":"2019","journal-title":"Eur. Urol."},{"key":"ref_4","first-page":"125","article-title":"Classification of prostatic carcinomas","volume":"50","author":"Gleason","year":"1966","journal-title":"Cancer Chemother. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/modpathol.3800054","article-title":"Gleason grading and prognostic factors in carcinoma of the prostate","volume":"17","author":"Humphrey","year":"2004","journal-title":"Mod. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/PAS.0000000000000530","article-title":"The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System","volume":"40","author":"Epstein","year":"2016","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Semba, R., Uchida, K., Hirokawa, Y., Shiraishi, T., Onishi, T., Sasaki, T., Inoue, T., and Watanabe, M. (2023). Short-term prognosis of low-risk prostate cancer patients is favorable despite the presence of pathological prognostic factors: A retrospective study. BMC Urol., 23.","DOI":"10.1186\/s12894-023-01345-z"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1002\/pros.24855","article-title":"Screening for Predictive Factors of Efficacy of Second-Generation Androgen Receptor Axis-Targeted Agents in Patients with High-Risk Metastatic Hormone-Sensitive Prostate Cancer","volume":"85","author":"Ueda","year":"2025","journal-title":"Prostate"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Inoue, T., Sekito, S., Kageyama, T., Sugino, Y., and Sasaki, T. (2023). Roles of the PARP Inhibitor in BRCA1 and BRCA2 Pathogenic Mutated Metastatic Prostate Cancer: Direct Functions and Modification of the Tumor Microenvironment. Cancers, 15.","DOI":"10.3390\/cancers15092662"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nature03445","article-title":"Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy","volume":"434","author":"Farmer","year":"2005","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"eaam7479","DOI":"10.1126\/scisignal.aam7479","article-title":"Androgen receptor inhibitor-induced \"BRCAness\" and PARP inhibition are synthetically lethal for castration-resistant prostate cancer","volume":"10","author":"Li","year":"2017","journal-title":"Sci. Signal."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lu, B., Liu, Y., Yao, Y., Yang, T., Zhang, H., Yang, X., Huang, R., Zhou, W., Pan, X., and Cui, X. (2024). Advances in sequencing and omics studies in prostate cancer: Unveiling molecular pathogenesis and clinical applications. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1355551"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Russo, P., Bizzarri, F.P., Filomena, G.B., Marino, F., Iacovelli, R., Ciccarese, C., Boccuto, L., Ragonese, M., Gavi, F., and Rossi, F. (2024). Relationship Between Loss of Y Chromosome and Urologic Cancers: New Future Perspectives. Cancers, 16.","DOI":"10.3390\/cancers16223766"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s12672-024-01399-x","article-title":"Exploring the interaction between immune cells in the prostate cancer microenvironment combining weighted correlation gene network analysis and single-cell sequencing: An integrated bioinformatics analysis","volume":"15","author":"Bavandi","year":"2024","journal-title":"Discov. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s12672-024-01277-6","article-title":"Precision molecular insights for prostate cancer prognosis: Tumor immune microenvironment and cell death analysis of senescence-related genes by machine learning and single-cell analysis","volume":"15","author":"Wu","year":"2024","journal-title":"Discov. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e27628","DOI":"10.1016\/j.heliyon.2024.e27628","article-title":"Identification of cell differentiation trajectory-related gene signature to reveal the prognostic significance and immune landscape in prostate cancer based on multiomics analysis","volume":"10","author":"Sun","year":"2024","journal-title":"Heliyon"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"43035","DOI":"10.18632\/oncotarget.17428","article-title":"Gene expression signature of Gleason score is associated with prostate cancer outcomes in a radical prostatectomy cohort","volume":"8","author":"Jhun","year":"2017","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s41391-018-0086-1","article-title":"Prevalence of DNA repair gene mutations in localized prostate cancer according to clinical and pathologic features: Association of Gleason score and tumor stage","volume":"22","author":"Marshall","year":"2019","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.2147\/IJGM.S321319","article-title":"Comprehensive Analysis and Identification of an Immune-Related Gene Signature with Prognostic Value for Prostate Cancer","volume":"14","author":"Zhang","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yimamu, Y., Yang, X., Chen, J., Luo, C., Xiao, W., Guan, H., and Wang, D. (2022). The Development of a Gleason Score-Related Gene Signature for Predicting the Prognosis of Prostate Cancer. J. Clin. Med., 11.","DOI":"10.3390\/jcm11237164"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5500416","DOI":"10.1155\/2022\/5500416","article-title":"Identification of the Key Genes Involved in the Tumorigenesis and Prognosis of Prostate Cancer","volume":"2022","author":"Wang","year":"2022","journal-title":"Comput. Math. Methods Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Filippi, A., Aurelian, J., and Mocanu, M.M. (2024). Analysis of the Gene Networks and Pathways Correlated with Tissue Differentiation in Prostate Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073626"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1007\/s00432-024-05899-9","article-title":"Establishment of a prognostic risk model for prostate cancer based on Gleason grading and cuprotosis related genes","volume":"150","author":"Wang","year":"2024","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1016\/j.csbj.2024.08.026","article-title":"UQCRB and LBH are correlated with Gleason score progression in prostate cancer: Spatial transcriptomics and experimental validation","volume":"23","author":"Quan","year":"2024","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/s41391-024-00825-z","article-title":"Targeting the tumor microenvironment, a new therapeutic approach for prostate cancer","volume":"28","author":"Fang","year":"2024","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hanzelmann, S., Castelo, R., and Guinney, J. (2013). GSVA: Gene set variation analysis for microarray and RNA-seq data. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-7"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.surg.2023.04.030","article-title":"E2F target score is associated with cell proliferation and survival of patients with hepatocellular carcinoma","volume":"174","author":"Chida","year":"2023","journal-title":"Surgery"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1097\/SLA.0000000000005954","article-title":"Intratumoral Tumor Infiltrating Lymphocytes (TILs) are Associated with Cell Proliferation and Better Survival But Not Always with Chemotherapy Response in Breast Cancer","volume":"278","author":"Wu","year":"2023","journal-title":"Ann. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/annonc\/mdx637","article-title":"Validation of a Metastatic Assay using biopsies to improve risk stratification in patients with prostate cancer treated with radical radiation therapy","volume":"29","author":"Jain","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Aran, D., Hu, Z., and Butte, A.J. (2017). xCell: Digitally portraying the tissue cellular heterogeneity landscape. Genome Biol., 18.","DOI":"10.1186\/s13059-017-1349-1"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.immuni.2018.03.023","article-title":"The Immune Landscape of Cancer","volume":"48","author":"Thorsson","year":"2018","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Guo, M., and Wang, S.M. (2022). The BRCAness Landscape of Cancer. Cells, 11.","DOI":"10.3390\/cells11233877"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/ijc.33988","article-title":"Identification of novel prostate cancer genes in patients stratified by Gleason classification: Role of antitumoral genes","volume":"151","author":"Zwir","year":"2022","journal-title":"Int. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/path.6057","article-title":"Automated Ki-67 labeling index assessment in prostate cancer using artificial intelligence and multiplex fluorescence immunohistochemistry","volume":"260","author":"Blessin","year":"2023","journal-title":"J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1159\/000519007","article-title":"High Inter- and Intratumoral Variability of Ki67 Labeling Index in Newly Diagnosed Prostate Cancer with High Gleason Scores","volume":"89","author":"Vlajnic","year":"2022","journal-title":"Pathobiology"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Niu, W., Zhang, T., and Ma, L. (2023). Correlation analysis between immune-related genes and cell infiltration revealed prostate cancer immunotherapy biomarkers linked to T cells gamma delta. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-28475-6"}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/7\/409\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:12:02Z","timestamp":1760033522000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/7\/409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,18]]},"references-count":36,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["curroncol32070409"],"URL":"https:\/\/doi.org\/10.3390\/curroncol32070409","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,18]]}}}