Intermediate-risk and high-risk localized prostate cancer are treatable, but metastases (in ~30% of patients) often lead to death. Immunotherapy shows promise for survival, but many patients do not respond, highlighting the need for biomarkers to predict metastases and treatment response.

In an article published in Scientific Reports, a novel indicator based on cell death was developed to predict metastases, biochemical recurrence (BCR) and immunotherapy response in prostate cancer. Prompted by the rationale that cell death pathways are crucial in metastases development, the authors used prostate adenocarcinoma data in The Cancer Genome Atlas (TCGA) to develop an eight-gene signature referred to as programmed cell death score (PCDS) based on differentially expressed genes associated with various programmed cell death mechanisms. Analysis of data from TCGA plus two validation cohorts showed that high PCDS is associated with aggressive tumour features, including increased metastases, T stage, grade and BCR, whereas low PCDS is associated with enhanced response to immunotherapy. A random forest analysis showed that, among the eight PCDS genes, the prostaglandin synthase PTGDS had the greatest influence on prostate cancer metastases. PTGDS expression was lower in metastatic versus non-metastatic prostate cancer tissue samples, and overexpression of PTGDS in prostate cancer cell lines reduced tumour cell migration, invasion and proliferation.

中危和高危局限性前列腺癌是可以治疗的，但转移（在 ~30% 的患者中）通常会导致死亡。免疫疗法显示出生存前景，但许多患者没有反应，这凸显了生物标志物来预测转移和治疗反应的必要性。

在发表在《科学报告》上的一篇文章中，开发了一种基于细胞死亡的新指标来预测前列腺癌的转移、生化复发 （BCR） 和免疫治疗反应。在细胞死亡途径在转移发展中至关重要的基本原理的推动下，作者使用癌症基因组图谱 （TCGA） 中的前列腺腺癌数据开发了一种称为程序性细胞死亡评分 （PCDS） 的八基因特征，该特征基于与各种程序性细胞死亡机制相关的差异表达基因。对来自 TCGA 和两个验证队列的数据的分析表明，高 PCDS 与侵袭性肿瘤特征相关，包括转移增加、T 分期、分级和 BCR，而低 PCDS 与对免疫治疗的反应增强相关。随机森林分析显示，在 8 个 PCDS 基因中，前列腺素合酶 PTGDS 对前列腺癌转移的影响最大。PTGDS 在转移性前列腺癌组织样本中的表达低于非转移性前列腺癌组织样本，PTGDS 在前列腺癌细胞系中的过表达减少了肿瘤细胞的迁移、侵袭和增殖。