Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA.
Department of Radiology, Stanford University, Stanford, CA, USA.
Br J Cancer. 2024 Dec;131(11):1748-1761. doi: 10.1038/s41416-024-02854-w. Epub 2024 Oct 14.
Despite nearly 100% 5-year survival for localised prostate cancer, the survival rate for metastatic prostate cancer significantly declines to 32%. Thus, it is crucial to identify molecular indicators that reflect the progression from localised disease to metastatic prostate cancer.
To search for molecular indicators associated with prostate cancer metastasis, we performed proteomic analysis of rapid autopsy tissue samples from metastatic prostate cancer (N = 8) and localised prostate cancer (N = 2). Then, we utilised multiple independent, publicly available prostate cancer patient datasets to select candidates that also correlate with worse prostate cancer clinical prognosis.
We identified 154 proteins with increased expressions in metastases relative to localised prostate cancer through proteomic analysis. From the subset of these candidates that correlate with prostate cancer recurrence (N = 28) and shorter disease-free survival (N = 37), we identified a 5-gene signature panel with improved performance in predicting worse clinical prognosis relative to individual candidates.
Our study presents a new 5-gene signature panel that is associated with worse clinical prognosis and is elevated in prostate cancer metastasis on both protein and mRNA levels. Our 5-gene signature panel represents a potential modality for the prediction of prostate cancer progression towards the onset of metastasis.
尽管局限性前列腺癌的 5 年生存率接近 100%，但转移性前列腺癌的生存率显著下降至 32%。因此，识别反映局限性疾病向转移性前列腺癌进展的分子指标至关重要。
为了寻找与前列腺癌转移相关的分子标志物，我们对转移性前列腺癌（N=8）和局限性前列腺癌（N=2）的快速尸检组织样本进行了蛋白质组学分析。然后，我们利用多个独立的、公开的前列腺癌患者数据集，选择与前列腺癌临床预后更差相关的候选标志物。
通过蛋白质组学分析，我们鉴定出 154 种在转移灶中表达升高的蛋白。在与前列腺癌复发（N=28）和无病生存期更短（N=37）相关的候选标志物亚集中，我们确定了一个由 5 个基因组成的标志物panel，其在预测更差的临床预后方面表现优于单个候选标志物。
我们的研究提出了一个新的与更差的临床预后相关的 5 个基因标志物panel，该标志物在蛋白和 mRNA 水平上均升高，与前列腺癌转移有关。我们的 5 个基因标志物panel 代表了一种潜在的预测前列腺癌向转移发生进展的模式。
