伦敦大学Gerhardt Attard研究组取得一项新突破。他们探明了肿瘤转录组全表达分类器预测晚期前列腺癌的治疗敏感性。这一研究成果于2025年8月26日发表在国际顶尖学术期刊《细胞》上。
为了确定新的生物标志物-治疗配对，课题组研究了在改变实践的3期试验（测试多西他赛或阿比特龙）中随机分配的患者的生物学途径与14年生存结果之间的关系。该课题组研究人员纳入了1523例（832例转移性）前列腺肿瘤的转录组表达特征和免疫组织化学标记（Ki-67和PTEN）。肿瘤雄激素受体信号与较长的生存期相关，而增殖增加则预示较短的生存期。
在一项预先指定的分析中，先前鉴定的破译RNA标记既可以预测多西紫杉醇治疗转移性癌症的预后，也可以预测多西紫杉醇的生存益处（生物标志物-多西紫杉醇相互作用p= 0.039）。此外，基于转录组的PTEN失活分类鉴定出更有可能发生PTEN蛋白丢失的肿瘤(p= 4 × 10-37)和代谢紊乱的转移性癌症，激素治疗的生存期较短（p< 0.001），但表现出多西他赛敏感性（生物标志物-多西他赛相互作用p= 0.002）。转录组分类器可预测多西他赛的疗效，并可用于临床改善患者管理。
据介绍，晚期前列腺癌对激素治疗有反应，但结果各不相同，没有预测治疗选择的试验。
附：英文原文
Title: Tumor transcriptome-wide expression classifiers predict treatment sensitivity in advanced prostate cancers
Author: Emily Grist, Peter Dutey-Magni, Marina A. Parry, Larissa Mendes, Ashwin Sachdeva, James A. Proudfoot, Anis A. Hamid, Mazlina Ismail, Sarah Howlett, Stefanie Friedrich, Lia DePaula Oliveira, Laura Murphy, Christopher Brawley, Oluwademilade Dairo, Sharanpreet Lall, Yang Liu, Daniel Wetterskog, Anna Wingate, Karolina Nowakowska, Leila Zakka, Claire L. Amos, Nafisah B. Atako, Victoria Wang, Hannah L. Rush, Robert J. Jones, Hing Leung, William R. Cross, Silke Gillessen, Chris C. Parker, Teresa Marafioti, Alfonso Urbanucci, Matthew Fittall, Edward M. Schaeffer, Daniel E. Spratt, David Waugh, Thomas Powles, Matthew R. Sydes, Felix Y. Feng, Daniel M. Berney, Mahesh K.B. Parmar, Noel W. Clarke, Elai Davicioni, Tamara L. Lotan, Christopher J. Sweeney, Louise C. Brown, Nicholas D. James, Gerhardt Attard
Issue&Volume: 2025-08-26
Abstract: Advanced prostate cancers respond to hormone therapy but outcomes vary and no predictive tests exist for informed treatment selection. To identify novel biomarker-treatment pairings, we examined associations between biological pathways and 14-year survival outcomes of patients randomized in practice-changing phase 3 trials (testing docetaxel or abiraterone). We included transcriptome-wide expression signatures and immunohistochemistry markers (Ki-67 and PTEN) on prostate tumors from 1,523 patients (832 metastatic). Tumor androgen receptor signaling is associated with longer survival, whereas increased proliferation predicted shorter survival. In a pre-specified analysis, the previously identified decipher RNA signature was both prognostic and predicted survival benefit from docetaxel for metastatic cancers (biomarker-docetaxel interaction p = 0.039). Additionally, transcriptome-based classification of PTEN inactivation identified tumors more likely to have PTEN protein loss (p = 4 × 1037) and metabolically perturbed metastatic cancers that had shorter survival with hormone therapies (p < 0.001) but exhibited docetaxel sensitivity (biomarker-docetaxel interaction p = 0.002). Transcriptome classifiers predict docetaxel benefit and could be clinically implemented for improved patient management.
DOI: 10.1016/j.cell.2025.07.042
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00864-5