Serum Insulin-Like Growth Factor Binding Protein 7 as a Potential Biomarker in the Diagnosis and Prognosis of Esophagogastric Junction Adenocarcinoma

Background/Aims@#Esophagogastric junction adenocarci-noma (EJA) is a malignant tumor associated with high mor-bidity and has attracted increasing attention due to a rising incidence and low survival rate. Pathological biopsy is the gold standard for diagnosis, but noninvasive and effective tests are lacking, resulting in diagnoses at advanced stages.This study explored the diagnostic value of insulin-like growth factor binding protein 7 (IGFBP7) in EJA. @*Methods@#A total of 120 EJA patients and 88 normal controls were recruited, and their serum levels of IGFBP7 were measured by enzymelinked immunosorbent assay. Receiver operating character-istic (ROC) curve analysis was used to assess the diagnostic value, and Pearson chi-square analysis was used to evaluate the correlation between IGFBP7 and clinical parameters. Ka-plan-Meier survival analysis was carried out to assess the ef-fect of IGFBP7 on overall survival (OS). @*Results@#The levels of IGFBP7 were higher in both early- and late-stage EJA patients than in normal controls (p<0.001). The area under the ROC curve for EJA patients was 0.794 (95% confidence interval [CI], 0.733 to 0.854), with a cutoff value of 2.716 ng/mL, a sensitivity of 63.3% (95% CI, 54.0% to 71.8%) and a specific-ity of 90.9% (95% CI, 82.4% to 95.7%). For the diagnosis of early-stage EJA, the same cutoff value and specificity were obtained, but the sensitivity of IGFBP7 was 54.3% (95% CI, 36.9% to 70.8%). Patients with low IGFBP7 protein expres-sion had lower OS than those with high expression (p=0.034).The multivariate analysis showed that IGFBP7 is an inde-pendent prognostic factor for EJA (p=0.011). @*Conclusions@#Serum IGFBP7 acts as a potential diagnostic and prognostic marker for EJA.

Inhibitory effect of ginsenoside Rg3 on the tube-like structure formation in human nasopharyngeal carcinoma HNE-1 cell line in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the anti-angiogenic effect of ginsenoside Rg3 (Rg3 in abbreviation) in human nasopharyngeal carcinoma HNE-1 cells in vitro.</p><p><b>METHODS</b>The tube-like structure (TLS) formation of HNE-1 cells, cultured in medium with different concentrations of Rg3, was determined by in vitro anti-angiogenic test based on preliminary experiment observing the TLSs formed by HNE-1 cells on Matrigel and their structural characteristics. The VEGF expression level in HNE-1 cells was determined by immunohistochemistry (IHC) and Western-blot test after 48-hour cultured in medium with different concentrations of Rg3.</p><p><b>RESULTS</b>HNE-1 cells could form TLSs and mosaic vessels when mix-cultured with CRL-2480 on Matrigel. Rg3 could inhibit the TLS formation of HNE-1 cells. After 24-hour culture in medium with Rg3 at concentrations of 0, 50, 100 and 200 µg/ml, the number of TLSs were 75.50 ± 6.86, 55.00 ± 11.92, 39.75 ± 7.93 and 24.50 ± 6.25, respectively, which were negatively correlated with the concentrations of Rg3 (r = -0.928; P < 0.01). After 48 hours of culture, the expressions of VEGF significantly declined by IHC test with results as 0.19 ± 0.03, 0.13 ± 0.02, 0.11 ± 0.01, and 0.08 ± 0.01, respectively, which were negatively correlated with the concentrations of Rg3 (r = -0.911; P < 0.01). The expressions of VEGF also gradually decreased as revealed by Western blot test, with corresponding results as 119.49, 111.51, 86.45, and 38.29. All of the tests showed significantly declined results in the group at the concentration of 200 µg/ml Rg3.</p><p><b>CONCLUSION</b>Rg3 can inhibit the vasculogenic mimicry of HNE-1 cells, and the possible mechanism might be associated with the down-regulation of VEGF protein expression in HNE-1 cells.</p>

Study on promoter methylation status of E-cadherin gene in nasopharyngeal carcinoma cell lines / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the role of methylation on E-cadherin inactivation in nasopharyngeal carcinoma (NPC) cell line HNE1 and CNE2, as well as evaluate the inhibitory effect of 5-aza-2'-deoxycytidine (5-Aza-dC) on cell abilities of proliferation and invasion.</p><p><b>METHODS</b>The expression level of E-cadherin was measured by RT-PCR, Western blot and immunohistochemistry (polymer method), the methyaltion status was analyzed by methylation-specific PCR (MSP), and cell proliferation and invasion were examined by MTT and invasion assay, separately before and after treatment with demethylating agent 5-Aza-dC.</p><p><b>RESULTS</b>The expression level of E-cadherin was down-regulated compared with the normal tissue, simultaneously partially methylated in gene promoter. Treatment with 20 µmol/L 5-Aza-dC increased the expression of E-cadherin and reduced the methylation degree. Moreover, it also significantly suppressed cell growth (27.6% for HNE1 cells and 34.3% for CNE2 cells, P < 0.05) and invasiveness (37.2% for HNE1 cells and 29.7% for CNE2 cells, P < 0.05).</p><p><b>CONCLUSIONS</b>Aberrant methylation around gene promoter region may play an important part in down regulation of E-cadherin in NPC, suggesting a potential therapeutic strategy for demethylating agents such as 5-Aza-dC.</p>