DNA 倍体和 PTEN 作为生物标志物,用于预测主动监测下的前列腺癌患者的侵袭性疾病。
DNA ploidy and PTEN as biomarkers for predicting aggressive disease in prostate cancer patients under active surveillance.
发表日期:2024 Jul 03
作者:
Karolina Cyll, Erik Skaaheim Haug, Manohar Pradhan, Ljiljana Vlatkovic, Birgitte Carlsen, Sven Löffeler, Wanja Kildal, Karin Skogstad, Frida Hauge Torkelsen, Rolf Anders Syvertsen, Hanne A Askautrud, Knut Liestøl, Andreas Kleppe, Håvard E Danielsen
来源:
BRITISH JOURNAL OF CANCER
摘要:
目前针对主动监测 (AS) 下的前列腺癌患者的风险分层工具可能不足以识别需要治疗的患者。我们研究了 DNA 倍体和 PTEN 作为预测 AS 患者侵袭性疾病的潜在生物标志物。我们通过图像细胞术评估了 DNA 倍体,并通过免疫组织化学评估了挪威当地医院 558 名 AS 患者的 3197 个含肿瘤组织块中的 DNA 倍体和 PTEN 蛋白表达。主要终点是治疗,治疗失败(生化复发或开始挽救治疗)作为次要终点。在单变量和多变量分析中,诊断时的组合 DNA 倍体和 PTEN (DPP) 状态与无治疗生存期相关, DPP 异常与 DPP 正常肿瘤的 HR 分别为 2.12 (p< 0.0001) 和 1.94 (p< 0.0001)。 DNA 倍体和 PTEN 状态与前列腺癌风险评估 (CAPRA) 评分的整合改善了风险分层(c 指数差异 = 0.025;p = 0.0033)。在接受治疗的患者中,患有 DPP 异常肿瘤的患者表现出治疗失败的可能性显着较高(HR 2.01;p = 0.027)。DNA 倍体和 PTEN 可以作为额外的生物标志物来识别 AS 患者发生侵袭性疾病的风险增加,从而使对最终将接受当前方案治疗的近 50% 的患者进行早期干预。© 2024。作者。
Current risk stratification tools for prostate cancer patients under active surveillance (AS) may inadequately identify those needing treatment. We investigated DNA ploidy and PTEN as potential biomarkers to predict aggressive disease in AS patients.We assessed DNA ploidy by image cytometry and PTEN protein expression by immunohistochemistry in 3197 tumour-containing tissue blocks from 558 patients followed in AS at a Norwegian local hospital. The primary endpoint was treatment, with treatment failure (biochemical recurrence or initiation of salvage therapy) as the secondary endpoint.The combined DNA ploidy and PTEN (DPP) status at diagnosis was associated with treatment-free survival in univariable- and multivariable analysis, with a HR for DPP-aberrant vs. DPP-normal tumours of 2.12 (p < 0.0001) and 1.94 (p < 0.0001), respectively. Integration of DNA ploidy and PTEN status with the Cancer of the Prostate Risk Assessment (CAPRA) score improved risk stratification (c-index difference = 0.025; p = 0.0033). Among the treated patients, those with DPP-aberrant tumours exhibited a significantly higher likelihood of treatment failure (HR 2.01; p = 0.027).DNA ploidy and PTEN could serve as additional biomarkers to identify AS patients at increased risk of developing aggressive disease, enabling earlier intervention for nearly 50% of the patients that will eventually receive treatment with current protocol.© 2024. The Author(s).