Background: Gleason score (GS) 10 prostate cancer (PC) is a highly aggressive localized disease. Despite advances in treating high-risk PC, the clinical outcomes and molecular underpinnings of GS 10 remain unclear. This study aimed to determine whether GS 10 PC has distinct clinical outcomes from other “high-risk” cancers (i.e., Gleason 8–9) and identify genomic alterations driving its aggressive phenotype.Methods: A retrospective review of The Cancer Genome Atlas database identified patients with GS 8–10 PC who underwent radical prostatectomy. Clinical factors were compared between GS 10 and GS 8–9 cohorts. Time to biochemical recurrence (BCR) was analyzed using Kaplan–Meier and Cox regression. RNA sequencing identified differentially expressed genes, and protein–protein interaction networks identified hub genes.Results: Of 192 patients, 13 (6.8%) had GS 10 PC. After median follow-up of 37.87 months, GS 10 status was associated with significantly lower time to BCR (AHR, 2.67; 95% CI, 1.18–6.02;p= 0.018) compared to GS 8–9. Multiple genes (e.g.,RAD54L,FAAH,AATK,MAST2) showed higher alteration frequencies, and high expression ofRAD54L,MAST2, andCCHCR1correlated with shorter disease-free survival. Six overlapping hub genes (CD8A,CDC20,E2F1,IL10,TNF,VCAM1) were overexpressed in GS 10 tumors, reflecting key pathways in tumor progression.Conclusions: GS 10 PC confers inferior time to BCR and displays a distinct genomic landscape compared to GS 8–9 disease, highlighting the need for biomarker-driven therapeutic strategies. Further studies are needed to validate these genomic targets and improve management for this very high-risk population.
背景：格里森评分（GS）10分的前列腺癌（PC）是一种高度侵袭性的局限性肿瘤。尽管高危前列腺癌的治疗已取得进展，但GS 10分前列腺癌的临床结局及其分子基础仍不明确。本研究旨在确定GS 10分前列腺癌是否具有与其他“高危”癌症（即格里森8-9分）不同的临床结局，并识别驱动其侵袭性表型的基因组改变。 方法：通过对癌症基因组图谱数据库进行回顾性分析，筛选出接受根治性前列腺切除术的GS 8-10分前列腺癌患者。比较GS 10分与GS 8-9分队列的临床因素。采用Kaplan-Meier法和Cox回归分析生化复发时间。通过RNA测序鉴定差异表达基因，并利用蛋白质-蛋白质相互作用网络识别枢纽基因。 结果：在192例患者中，13例（6.8%）为GS 10分前列腺癌。中位随访37.87个月后，与GS 8-9分相比，GS 10分状态与显著更短的生化复发时间相关（调整后风险比，2.67；95%置信区间，1.18–6.02；p=0.018）。多个基因（如RAD54L、FAAH、AATK、MAST2）显示出更高的改变频率，且RAD54L、MAST2和CCHCR1的高表达与较短的无病生存期相关。六个重叠的枢纽基因（CD8A、CDC20、E2F1、IL10、TNF、VCAM1）在GS 10分肿瘤中过表达，反映了肿瘤进展的关键通路。 结论：与GS 8-9分疾病相比，GS 10分前列腺癌具有更差的生化复发时间，并展现出独特的基因组特征，这凸显了基于生物标志物的治疗策略的必要性。需要进一步研究验证这些基因组靶点，以改善对这一极高危人群的管理。
Clinical Outcomes and Genomic Alterations in Gleason Score 10 Prostate Cancer
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