Knockdown of Decoy Receptor 3 Impairs Growth and Invasiveness of Hepatocellular Carcinoma Cell Line of HepG2 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Decoy receptor 3 (DcR3) binds to Fas ligand (FasL) and inhibits FasL-induced apoptosis. The receptor is overexpressed in hepatocellular carcinoma (HCC), and it is associated with the growth and metastatic spread of tumors. DcR3 holds promises as a new target for the treatment of HCC, but little is known regarding the molecular mechanisms underlying the oncogenic properties of DcR3. The present work, therefore, examined the role of DcR3 in regulating the growth and invasive property of liver cancer cell HepG2.</p><p><b>METHODS</b>HepG2 cells were stably transfected with lentivirus-based short hairpin RNA vector targeting DcR3. After the knockdown of DcR3 was confirmed, cell proliferation, clone formation, ability of migrating across transwell membrane, and wound healing were assessed in vitro. Matrix metalloproteinase-9 (MMP 9) and vascular epithelial growth factor (VEGF)-C and D expressions of the DcR3 knockdown were also studied. Comparisons between multiple groups were done using one-way analysis of variance (ANOVA), while pairwise comparisons were performed using Student's t test. P< 0.05 was regarded statistically significant.</p><p><b>RESULTS</b>DcR3 was overexpressed in HepG2 compared to other HCC cell lines and normal hepatocyte Lo-2. Stable knockdown of DcR3 slowed down the growth of HepG2 (P < 0.05) and reduced the number of clones formed by 50% compared to those without DcR3 knockdown (P < 0.05). The knockdown also reduced the migration of HepG2 across transwell matrix membrane by five folds compared to the control (P < 0.05) and suppressed the closure of scratch wound (P < 0.05). In addition, the messenger RNA levels of MMP 9, VEGF-C, and VEGF-D were significantly suppressed by DcR3 knockdown by 90% when compared with the mock control (P < 0.05).</p><p><b>CONCLUSIONS</b>Loss of DcR3 impaired the growth and invasive property of HCC cell line of HepG2. Targeting DcR3 may be a potential therapeutic approach for the treatment of HCC.</p>

Association of serum decoy receptor 3 protein level with the clinicopathologic features of bladder transitional cell carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the association of serum levels of decoy receptor 3(DcR3) protein and the clinicopathologic features of bladder transitional cell carcinoma.</p><p><b>METHODS</b>Enzyme-linked immunosorbent assay was used to examine the serum levels of DcR3 in patients with bladder transitional cell carcinoma for analysis of its association with the patients' age, gender, clinical stages and pathological classification.</p><p><b>RESULTS</b>The patients with bladder transitional cell carcinoma showed a significantly elevated serum level of DcR3 (183.43 ∓78.45 pg/m1) compared with the normal level (116.65∓97.43 pg/m1, P<0.05). The serum level of DcR3 in the patients showed close correlations with the TNM stage and pathological classification of the tumor (P<0.05) but not with the patients' age or gender (P>0.05).</p><p><b>CONCLUSIONS</b>In patients with bladder transitional cell carcinoma, a high serum level of DcR3 suggests a higher malignancy of the tumor.</p>

The expression of EMS1 and DcR3 protein in laryngeal carcinoma and the relation between EMS1 and DcR3 / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the expression of EMS1 and DcR3 in laryngeal carcinoma and analyze the relation of EMS1 and DcR3.@*METHOD@#The expression of EMS1 and DcR3 protein in 41 laryngeal carcinoma fresh samples and 41 para-carcinoma tissues (to cutting margin > 0.5 cm) were measured by flow cytometry, and 15 normal laryngeal mucosa samples were also studied as controls.@*RESULT@#(1) The quantitative and qualitative expression of EMS1 and DcR3 protein in laryngeal carcinoma tissues was obviously higher than those in para-carcinoma and in normal laryngeal mucosa tissues respectively (P < 0.05). There was no significant difference between the expression of para-carcinoma and normal laryngeal mucosa tissues. (2) In laryngeal carcinoma, the expression of EMS1 and DcR3 protein was independent of patients' clinical classification, tumor size, smoking history, patients' age and sex but associated with tumor metastasis, pathological grade and clinical stage. (3) In laryngeal carcinoma, the expression of EMS1 was positively correlated with that of DcR3.@*CONCLUSION@#EMS1 was positively related to DcR3, which might play an important role in the carcinogenesis and development of laryngeal carcinoma by synergic effect.

Expression of decoy receptor 3 in liver tissue microarrays.

Background. Decoy receptor 3 (DcR3), a new member of the tumour necrosis factor receptor (TNFR) superfamily, is amplified and overexpressed in various cancers. We investigated the expression of DcR3 protein in liver tissue microarrays and assessed its importance in patients with hepatocellular carcinoma (HCC). Methods. In this retrospective study, tissue from 120 patients with HCC, 48 with tissue at least 2 cm away from the tumour (juxta-tumour tissue), 62 with cirrhosis and 23 with normal livers were studied as tissue microarrays. Immunohistochemistry was used to detect the expression of DcR3. Statistical analyses were done to assess the association between DcR3 expression and the clinicopathological features of HCC. Results. The positivity rate of DcR3 in HCC tissue was significantly higher than that in juxta-tumour tissue, cirrhosis and normal liver (p=0.017, p<0.0001, p<0.0001, respectively). The positive rate of DcR3 in juxta-tumour and cirrhotic tissue both increased significantly when compared with normal liver tissue (p<0.0001, p=0.005, respectively). The positivity rate of DcR3 in HCC in clinical TNM stages I and II was significantly lower than that in stages III and IV (p<0.0001). The positivity rate of DcR3 in patients without metastasis within 20 months decreased significantly compared with those with metastasis (p<0.0001). DcR3 expression in patients with alphafoetoprotein levels >400 g/L, portal vein tumour emboli, capsular infiltration and multicentric tumour was significantly higher than in groups without these features (p=0.021, p<0.0001, p<0.0001, p=0.002, respectively). Conclusion. The overexpression of DcR3 might play an important role in the pathogenesis, progression and metastases of HCC. The DcR3 gene might serve as an important molecular biological indicator in diagnosing and predicting the biological behaviour of patients with HCC.

Relationship between expression of decoy receptor 3 and apoptosis in hepatocellular carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of decoy receptor 3 (DcR3) and its relationship with apoptosis and prognosis in hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>The expression of DcR3 protein in 43 cases of HCC and 16 cases of non-cancerous liver (including cirrhotic liver tissue and normal liver tissue adjacent to cavernous hemangioma) was studied by immunohistochemistry (using EnVision method). The status of apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) technique. Statistic analysis was carried out to assess the correlation between DcR3 expression, apoptotic index (AI) and clinicopathologic parameters.</p><p><b>RESULTS</b>DcR3 protein was expressed in the cytoplasm of HCC cells. The positivity rate of DcR3 in HCC was 74.42% (32/43), which was significantly higher than that in the non-cancerous group (43.75%, P < 0.05). The positivity rate of DcR3 in HCC with metastasis detected within 20 months of diagnosis was 100% (22/22). This was significantly higher than that in HCC without metastasis (52.94%, P < 0.01). The DcR3 expression in HCC also correlated with serum alpha-fetoprotein level (r = 0.444, P < 0.01) and presence of tumor embolus in portal vein (r = 0.414, P < 0.01). However it had no relationship with the patient's age, sex, cirrhotic status, liver capsule invasion, number of tumor nodules and histologic differentiation (P > 0.05). The AI in HCC (0.78 +/- 0.64)% was significantly lower than that in the non-cancerous group [(3.32 +/- 1.81)%, P < 0.01]. The AI in clinical TNM stage I and II tumors (1.03 +/- 0.69)% was significantly higher than that in stage III and IV tumors [(0.52 +/- 0.48)%, P < 0.01]. The AI in HCC without metastasis (1.10 +/- 0.72)% was significantly higher than that in HCC without metastasis [(0.44 +/- 0.27)%, P < 0.05]. The AI correlated with serum alpha-fetoprotein level (r = -0.468, P < 0.01), presence of tumor embolus in portal vein (r = -0.434, P < 0.01) and liver capsule invasion (r = -0.331, P < 0.05). On the other hand, it had no relationship with patient's age, sex, cirrhotic status, number of tumor nodules and histologic differentiation (P > 0.05). The AI in DcR3-positive group (including both HCC and non-cancerous tissues) was significantly lower than that in DcR3-negative group (P < 0.01).</p><p><b>CONCLUSIONS</b>The expression of DcR3 in HCC correlates with apoptosis of tumor cells and may play a crucial role in tumor pathogenesis and progression. DcR3 protein expression and AI may also serve as important biologic indicators in predicting prognosis of HCC.</p>

Expression of DcR3 protein and its significance in laryngeal carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the expression of DcR3 in laryngeal carcinoma and analyze the relation between DcR3 and clinical factors.@*METHOD@#The expression of DcR3 protein in 41 laryngeal carcinoma tissues and 41 para-carcinoma tissues (to cutting margin > 0.5 cm) were measured by Flow Cytometer(Epics-XL II), 15 normal laryngeal mucosa tissues were served as controls.@*RESULT@#(1) The quantitative and qualitative expression of DcR3 protein in laryngeal carcinoma tissues was obviously higher than those in para-carcinoma and normal laryngeal mucosa tissues, respectively (P < 0.05). There was no significant difference for the DcR3 protein expression between para-carcinoma and normal laryngeal mucosa tissues. (2) In laryngeal carcinoma, the expression of DcR3 protein was not significantly related to clinical classification, tumor size, smoking history, patients' age and sex but related to metastasis, pathological grade and clinical stage.@*CONCLUSION@#The high level of DcR3 expression may contribute to the carcinogenesis and development of laryngeal carcinoma. So it can be an important index for judging the differentiation, infiltration, metastasis and staging of laryngeal carcinoma.

Clinical significance and correlation between elevated serum TR6 and lympho-metastasis in gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the value of serum TR(6) for the diagnosis and TNM classification in patients with gastric carcinoma.</p><p><b>METHODS</b>Serum TR(6) levels were measured using ELISA method in 31 gastric cancer patients, 19 patients with nonmalignant conditions and 29 healthy individuals. TR(6) expression in tumor mass was studied with immunohistochemistry. TR(6) gene copy number in tumor tissues was evaluated by real time PCR.</p><p><b>RESULTS</b>Ninety-seven point nine percent (47 of 48 cases) of healthy individuals and patients with nonmalignant conditions were serum TR(6)-negative. In contrast, 71% (22 of 31 cases) of gastric cancer patients were serum TR(6)-positive. Serum TR(6) positiveness was closely correlated with tumor differentiation status and TNM classification. TR(6) gene amplification did not occur in gastric carcinoma.</p><p><b>CONCLUSIONS</b>Serum TR(6) levels were correlated significantly with TNM stage and histopathological type of tumor. This can help to determine the pre-operative TNM classification and to choose the optimal extent of lymph node dissection for gastric cancer.</p>