Prostate cancer invasion and metastasis: insights from mining genomic data
Prostate cancer invasion and metastasis: insights from mining genomic data
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DOI：
10.1093/bfgp/elt021
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发表时间：
2013-09-01
影响因子：
4
通讯作者：
Loots, Gabriela G.
中科院分区：
文献类型：
--
作者：
Hudson, Bryan D.;Kulp, Kristen S.;Loots, Gabriela G.
前列腺癌（PCa）是西方世界男性中第二大最常见的恶性肿瘤，也是全球男性癌症相关死亡的第二大原因。虽然大多数癌症在适当的条件下有转移的潜力，但PCa倾向于骨骼作为转移的主要部位，这表明骨微环境有利于其生长。PCa转移通过一系列复杂的分子事件进行，包括原始肿瘤部位的血管生成、原发部位内的局部迁移、向血流中的内渗、循环内的存活、肿瘤细胞向靶器官的外渗以及这些细胞在新部位内的定殖。反过来，这些步骤中的每一个都涉及利用多种蛋白质-蛋白质相互作用、蛋白质信号级联和转录变化的复杂事件链。尽管迫切需要改善目前用于诊断、预后和耐药性的生物标志物，但进展缓慢。基因微阵列和RNA测序等全球基因表达方法使科学家能够同时研究数千个基因，并使科学家能够研究癌症发病机制的分子途径。在这篇综述中，我们总结了目前的文献，探讨高通量转录组分析对前列腺癌的生物标志物发现的进步。迫切需要新的生物标志物来实现PCa的更准确检测，改善肿瘤侵袭性的预测，并促进为定制药物发现新的治疗靶点。从基因表达谱研究中鉴定出的有希望的分子标记包括HPN、CLU 1、WT 1、WNT 5A、AURKA和HPN。
Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men in the Western world and the second leading cause of cancer-related deaths among men worldwide. Although most cancers have the potential to metastasize under appropriate conditions, PCa favors the skeleton as a primary site of metastasis, suggesting that the bone microenvironment is conducive to its growth. PCa metastasis proceeds through a complex series of molecular events that include angiogenesis at the site of the original tumor, local migration within the primary site, intravasation into the blood stream, survival within the circulation, extravasation of the tumor cells to the target organ and colonization of those cells within the new site. In turn, each one of these steps involves a complicated chain of events that utilize multiple protein-protein interactions, protein signaling cascades and transcriptional changes. Despite the urgent need to improve current biomarkers for diagnosis, prognosis and drug resistance, advances have been slow. Global gene expression methods such as gene microarrays and RNA sequencing enable the study of thousands of genes simultaneously and allow scientists to examine molecular pathways of cancer pathogenesis. In this review, we summarize the current literature that explored high-throughput transcriptome analysis toward the advancement of biomarker discovery for PCa. Novel biomarkers are strongly needed to enable more accurate detection of PCa, improve prediction of tumor aggressiveness and facilitate the discovery of new therapeutic targets for tailored medicine. Promising molecular markers identified from gene expression profiling studies include HPN, CLU1, WT1, WNT5A, AURKA and SPARC.