研究發(fā)現(xiàn),卵巢癌患者血清內(nèi)死亡受體6(DR6)蛋白水平升高,。近日,,美國密歇根大學(xué)的研究人員在幾種上皮性癌及肉瘤中測試了DR6血清蛋白水平,以此來尋找有效的肉瘤診斷/預(yù)測性生物標(biāo)記物,。相關(guān)論文發(fā)表在5月2日的PLoS ONE,。
通過篩查實體瘤DR6基因表達(dá)譜,以及對子宮癌肉瘤、膀胱癌,、肝癌以及胰腺癌患者及健康對照組血清蛋白的定量熒光免疫蛋白印跡分析,,DR6血清水平變化被用來分析DR6作為肉瘤響應(yīng)治療的能力。
研究發(fā)現(xiàn),,在所有的被測試的腫瘤類型,,DR6的mRNA均高表達(dá)。與健康對照組相比,,在子宮癌肉瘤,、膀胱癌、肝癌或者是前列腺癌患者中DR6血清水平?jīng)]有明顯升高,。
但是,,來自成熟肉瘤病人的血清DR6蛋白水平被明顯升高(p<0.001),尤其在滑膜肉瘤中蛋白水平升高非常顯著,。而且,,在治療期間血清DR6蛋白水平變化與治療的臨床受益一致,。
因此,,對一些成熟肉瘤亞型,DR6很可能會成為一個臨床有效的診斷及預(yù)測型血清生物標(biāo)記物,。由于肉瘤的診斷十分困難,,而錯誤診斷會干擾對癌癥的有效控制。DR6血清蛋白的應(yīng)用很可能會幫助診斷并改善治療計劃,。
對處于進展期腫瘤的患者,,升高的DR6水平表明腫瘤對治療無應(yīng)答,這可避免醫(yī)生過分依賴醫(yī)學(xué)影像,,加快有效治療方案的決策,。(生物谷Deepblue編譯)
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.