DR6 as a Diagnostic and Predictive Biomarker in Adult Sarcoma

Abstract

BackgroundThe 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.MethodsDR6 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.ResultsDR6 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%).ConclusionDR6 may be a clinically useful diagnostic and predictive serum biomarker for some adult sarcoma subtypes.ImpactDiagnosis 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.

Breast Carcinoma Progression and Tumour Vascular Markers Related to Apoptotic Mechanisms

“…Our results as well correlate with Yang et al [26] who detected overexpression (125%) of DR6 mRNA in patients suffering from ductal invasive carcinoma.…”

Inhibition of IRE1 modifies effect of glucose deprivation on the expression of TNF?-related genes in U87 glioma cells

“…Moreover, B-cells lacking TNFRSF21/DR6 show the increased proliferation rate and cell survival upon mitogenic stimulation [25]. However, this gene is highly expressed in many tumor cell lines and tumor samples [25,26]. Thus, the role of TNFRSF21/DR6 as an apoptosisinducing receptor is less clear and perhaps cell type dependent and needs further investigation.…”

“…Recently it was also shown that TNFRSF10B/TRAILR2 inhibits maturation of the microRNA let-7 and increases proliferation of pancreatic cancer cell lines and other tumor cells [22]. Moreover, the expression of TRAIL receptors is greatly elevated in many cancer types, suggesting that tumors benefit from the expression of these receptors [25,26]. To date, the majority of studies on експериментальні роботи…”

“…However, sporadic reports also suggest that TRAIL receptors can lead to other outcomes such as cytokine and chemokine production, cell proliferation and cell migration. Indeed, although transformed cells frequently express TRAIL, most do not undergo apoptosis upon engagement of these receptors and significant effort has been devoted toward exploring how to sensitize such cells to the pro-apoptotic effects of death receptor stimulation [25][26][27][28][29].…”

“…However, sporadic reports also suggest that engagement of the TRAIL receptors can lead to other outcomes such as cytokine and chemokine production, cell proliferation, cell migration and differentiation. Indeed, although transformed cells frequently express TRAIL, most do not undergo apoptosis upon engagement of these receptors and significant effort has been devoted toward exploring how to sensitize such cells to the pro-apoptotic effects of death receptor stimulation [25][26][27][28][29]. Moreover, the expression of TRAIL receptors is greatly elevated in many cancer types such as hepatocellular carcinoma, renal carcinoma and ovarian cancer, suggesting that such tumors benefit from the expression of these receptors [25,6].…”