Clinical significance of detecting elevated serum DcR3/TR6/M68 in malignant tumor patients.
TR6/DcR3/M68 is a soluble receptor that belongs to the TNF receptor family. It is expressed in malignant cells of several tumor types and has been postulated to help tumor cells to gain survival advantage by inhibiting apoptosis and by interfering with immune surveillance. In our study, we assessed for the first time serum TR6 in tumor patients to explore its diagnostic and prognostic value. We examined serum TR6 levels with ELISA in 146 tumor patients, 19 patients with acute infection, 5 patients with liver cirrhosis and 29 healthy individuals. TR6 expression in tumor mass was studied with immunohistochemistry. TR6 gene copy number in tumor tissues was evaluated by real time PCR. Ninety-seven point nine percent (47 of 48 cases) of healthy individuals and patients with acute infection were serum TR6-negative. In contrast, 56.2% (82 of 146 cases) of the tumor patients were serum TR6-positive. Almost all serum TR6-positive individuals (98.8%, 82 out of 83 cases) had malignancy, excluding the cases of liver cirrhosis. In gastric carcinomas, serum TR6 levels were closely correlated with tumor differentiation status and TNM classification. Tumor mass was the source of serum TR6 because its levels decreased drastically after curative tumor resection. TR6 gene amplification occurred in about half of liver carcinomas, but not in gastric or pancreatic carcinomas, indicating plural mechanisms of TR6 upregulation. Our study demonstrated that serum TR6 should be considered as a novel parameter for the diagnosis, treatment and prognosis of malignancies.
Laboratory of Transplantation Immunology, Research Center, Centre Hospitalier de l'Universite de Montreal (CHUM)-Notre Dame Hospital, 1560 Sherbrooke Street East, Montreal, Quebec H2L 4M1, Canada.
Yulian
Y
Wu
Bing
B
Han
Hongwei
H
Sheng
Min
M
Lin
Paul A
PA
Moore
Jun
J
Zhang
Jiangping
J
Wu
D018263:Adenocarcinoma, Follicular / Q000097:blood / Q000473:pathology; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000097:blood / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology; D002277:Carcinoma / Q000097:blood / Q000473:pathology; D002454:Cell Differentiation; D003199:Computer Systems; D004067:Digestive System Neoplasms / Q000097:blood / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007239:Infections / Q000097:blood; D007822:Laryngeal Neoplasms / Q000097:blood / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology; D008562:Membrane Glycoproteins / Q000097:blood*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000097:blood*; D009369:Neoplasms / Q000097:blood* / Q000473:pathology; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D012509:Sarcoma / Q000097:blood / Q000473:pathology; D013964:Thyroid Neoplasms / Q000097:blood / Q000473:pathology
D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human