Samaržija Ivana, Konjevoda Paško
Laboratory for Epigenomics, Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia.
Biomedicines. 2023 Jul 15;11(7):2006. doi: 10.3390/biomedicines11072006.
Prostate cancer is a heterogeneous disease, and one of the main obstacles in its management is the inability to foresee its course. Therefore, novel biomarkers are needed that will guide the treatment options. The extracellular matrix (ECM) is an important part of the tumor microenvironment that largely influences cell behavior. ECM components are ligands for integrin receptors which are involved in every step of tumor progression. An underlying characteristic of integrin activation and ligation is the formation of integrin adhesion complexes (IACs), intracellular structures that carry information conveyed by integrins. By using The Cancer Genome Atlas data, we show that the expression of ECM- and IACs-related genes is changed in prostate cancer. Moreover, machine learning methods revealed that they are a source of biomarkers for progression-free survival of patients that are stratified according to the Gleason score. Namely, low expression of and high expression of genes are associated with worse survival of patients with a Gleason score lower than 9. The gene encodes protein that may play a role in the assembly of the ECM and the gene product is a protein tyrosine phosphatase activated by integrins. Our results suggest potential biomarkers of prostate cancer progression.
前列腺癌是一种异质性疾病，其治疗的主要障碍之一是无法预测其病程。因此，需要新的生物标志物来指导治疗方案的选择。细胞外基质（ECM）是肿瘤微环境的重要组成部分，在很大程度上影响细胞行为。ECM成分是整合素受体的配体，参与肿瘤进展的每一个步骤。整合素激活和连接的一个基本特征是形成整合素黏附复合物（IACs），这是一种携带整合素传递信息的细胞内结构。通过使用癌症基因组图谱数据，我们发现前列腺癌中与ECM和IACs相关的基因表达发生了变化。此外，机器学习方法表明，它们是根据Gleason评分分层的患者无进展生存期生物标志物的来源。具体而言，基因的低表达和基因的高表达与Gleason评分低于9的患者较差的生存率相关。基因编码的蛋白质可能在ECM的组装中起作用，基因产物是一种由整合素激活的蛋白质酪氨酸磷酸酶。我们的结果提示了前列腺癌进展的潜在生物标志物。
