DR6能作为肉瘤的诊断及预测生物标记物

研究发现，卵巢癌患者血清内死亡受体6(DR6)蛋白水平升高。近日，美国密歇根大学的研究人员在几种上皮性癌及肉瘤中测试了DR6血清蛋白水平，以此来寻找有效的肉瘤诊断/预测性生物标记物。相关论文发表在5月2日的PLoS ONE。

通过筛查实体瘤DR6基因表达谱，以及对子宫癌肉瘤、膀胱癌、肝癌以及胰腺癌患者及健康对照组血清蛋白的定量荧光免疫蛋白印迹分析，DR6血清水平变化被用来分析DR6作为肉瘤响应治疗的能力。

研究发现，在所有的被测试的肿瘤类型，DR6的mRNA均高表达。与健康对照组相比，在子宫癌肉瘤、膀胱癌、肝癌或者是前列腺癌患者中DR6血清水平没有明显升高。

但是，来自成熟肉瘤病人的血清DR6蛋白水平被明显升高(p<0.001)，尤其在滑膜肉瘤中蛋白水平升高非常显著。而且，在治疗期间血清DR6蛋白水平变化与治疗的临床受益一致。

因此，对一些成熟肉瘤亚型，DR6很可能会成为一个临床有效的诊断及预测型血清生物标记物。由于肉瘤的诊断十分困难，而错误诊断会干扰对癌症的有效控制。DR6血清蛋白的应用很可能会帮助诊断并改善治疗计划。

对处于进展期肿瘤的患者，升高的DR6水平表明肿瘤对治疗无应答，这可避免医生过分依赖医学影像，加快有效治疗方案的决策。（生物谷Deepblue编译）

doi: 10.1371/journal.pone.0036525
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DR6 as a Diagnostic and Predictive Biomarker in Adult Sarcoma

Kun Yang, Colin Mooney, Greg Spahlinger, Scott Schuetze, Hugo Arias-Pulido, Claire Verschraegen, Phyllis Gimotty, Ronald J. Buckanovich.

The Death Receptor 6 (DR6) protein is elevated in the serum of ovarian cancer patients. We tested DR6 serum protein levels as a diagnostic/predictive biomarker in several epithelial tumors and sarcomas.DR6 gene expression profiles were screened in publically available arrays of solid tumors. A quantitative immunofluorescent western blot analysis was developed to test the serum of healthy controls and patients with sarcoma, uterine carcinosarcoma, bladder, liver, and pancreatic carcinomas. Change in DR6 serum levels was used to assay the ability of DR6 to predict the response to therapy of sarcoma patients.DR6 mRNA is highly expressed in all tumor types assayed. Western blot analysis of serum DR6 protein demonstrated high reproducibility (r = 0.97). Compared to healthy donor controls, DR6 serum levels were not elevated in patients with uterine carcinosarcoma, bladder, liver, or pancreatic cancers.Serum DR6 protein levels from adult sarcoma patients were significantly elevated (p<0.001). This was most evident for patients with synovial sarcoma. Change in serum DR6 levels during therapy correlated with clinical benefit from therapy (sensitivity 75%, and positive predictive value 87%).DR6 may be a clinically useful diagnostic and predictive serum biomarker for some adult sarcoma subtypes.Diagnosis of sarcoma can be difficult and can lead to improper management of these cancers. DR6 serum protein may be a tool to aid in the diagnosis of some sarcomatous tumors to improve treatment planning.For patients with advanced disease, rising DR6 levels predict non-response to therapy and may expedite therapeutic decision making and reduce reliance on radiologic imaging.