PNAS：前列腺癌复发新的生物标志物SPARCL1

在一项研究前列腺癌细胞的生长和演变成更具侵略性的肿瘤细胞过程中，约翰霍普金斯大学泌尿科医生发现，一个特定的蛋白质的减少与前列腺癌侵略性相关，该蛋白可作为一个生物标志物来预示癌症复发风险的增加。他们的研究结果发表在8月27日的PNAS杂志上。

该团队专注于一个称为SPARCL1的基因，SPARCL1基因似乎对胚胎前列腺发育中细胞的迁移过程以及癌症的发展过程中是非常重要的。通常情况下，良性和恶性前列腺癌的细胞表达高水平的SPARCL1，但当前列腺癌细胞发生迁移时，这一基因的表达水平会降低。团队认为SPARCL1表达的减少或下调与前列腺癌的侵略性相关。

约翰霍普金斯大学医学院泌尿外科，肿瘤学和病理学的主任Edward Schaeffer医学博士称我们的研究结果让医生不仅能得知哪些癌症患者在手术后会注定要复发，同时也揭示了潜在的新的治疗方法。

在他们的研究中，Schaeffer和Paula Hurley博士还发现，SPARCL1似乎在预测肿瘤复发中发挥作用，包括膀胱癌，乳腺癌，结肠癌，直肠癌，肺癌，舌，皮肤，卵巢癌。该小组目前正在破译其具体机制，试图通过控制该基因来开发出一种可以重置SPARCL1于正常水平，从而防止癌症病人复发的治疗手段。

Hurley目前正在调查，该基因是否不仅适用于致命性前列腺癌的预后，同时是否也有助于前列腺癌进展的预测。据美国癌??症协会预计，在美国大约240,000人被诊断出患有前列腺癌，今年被诊断出的患者大部分是65岁以上。这种疾病是美国男性死亡的第二大原因。今年，在美国，估计有28,000人死于前列腺癌。Schaeffer表示；虽然我们许多患者最初用手术得到了治愈，但仍有一些癌症患者出现了复发现象。对于较高复发风险的患者，我们的最终目标是开发新的治疗防止癌症复发。

doi:10.1073/pnas.1203525109
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Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical outcome

Paula J. Hurleya,1, Luigi Marchionnib, Brian W. Simonsc,d, Ashley E. Rossa,b,d, Sarah B. Peskoee, et al.

Prostate cancer is the second leading cause of cancer death among United States men. However, disease aggressiveness is varied, with low-grade disease often being indolent and high-grade cancer accounting for the greatest density of deaths. Outcomes are also disparate among men with high-grade prostate cancer, with upwards of 65% having disease recurrence even after primary treatment. Identification of men at risk for recurrence and elucidation of the molecular processes that drive their disease is paramount, as these men are the most likely to benefit from multimodal therapy. We previously showed that androgen-induced expression profiles in prostate development are reactivated in aggressive prostate cancers. Herein, we report the down-regulation of one such gene, Sparcl1, a secreted protein, acidic and rich in cysteine (SPARC) family matricellular protein, during invasive phases of prostate development and regeneration. We further demonstrate a parallel process in prostate cancer, with decreased expression of SPARCL1 in high-grade/metastatic prostate cancer. Mechanistically, we demonstrate that SPARCL1 loss increases the migratory and invasive properties of prostate cancer cells through Ras homolog gene family, member C (RHOC), a known mediator of metastatic progression. By using models incorporating clinicopathologic parameters to predict prostate cancer recurrence after treatment, we show that SPARCL1 loss is a significant, independent prognostic marker of disease progression. Thus, SPARCL1 is a potent regulator of cell migration/invasion and its loss is independently associated with prostate cancer recurrence.