Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma.

AIM: To determine the prevalence and diagnostic value of autoantibodies in α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC). METHODS: Fifty-six serum samples from AFP-negative HCC cases, 86 from AFP-positive HCC cases, 168 from chronic liver disease cases, and 59 from normal human controls were included in this study. Autoantibodies to nucleophosmin (NPM)1, 14-3-3zeta and mouse double minute 2 homolog (MDM2) proteins in AFP-negative HCC serum were evaluated by enzyme-linked immunosorbent assay. Partially positive sera were further evaluated by western blotting. Immunohistochemistry was used to detect the expression of three tumor-associated antigens (TAAs) in AFP-negative HCC and normal control tissues. RESULTS: The frequency of autoantibodies to the three TAAs in AFP-negative HCC sera was 21.4%, 19.6% and 19.6%, which was significantly higher than in the chronic liver disease cases and normal human controls (P < 0.01) as well as AFP-positive HCC cases. The sensitivity of the three autoantibodies for diagnosis of AFP-negative HCC ranged from 19.6% to 21.4%, and the specificity was approximately 95%. When the three autoantibodies were combined, the sensitivity reached 30.4% and the specificity reached 91.6%. CONCLUSION: Autoantibodies to NPM1, 14-3-3zeta and MDM2 may be useful biomarkers for immunodiagnosis of AFP-negative HCC.

[Expression of CXCR7 in Gastric Cancer Cells and Its Effect on the Migration and Invasion of SGC-7901 Cells].

OBJECTIVES: To determine the expression of chemokine (C-X-C motif) receptor 7 (CXCR7) in five gastric cancer cell lines with various degrees of differentiation, and the effect of silencing CXCR7 on the migration and invasion of SGC-7901 cells. METHODS: The expression of CXCR7 in gastric cell lines (HGC-27, MGC-803, SGC-7901, BGC-823 and MKN-28) was detected by Western bolt and RT-PCR. The SGC-7901 cells were transfected with liposome of CXCR7 siRNA to silence CXCR7 gene, and then treated with stromal-derived factor-1 (SDF-1)-the ligand of CXCR7. Transwell assay was used for determining the migratory and invasive ability of SGC-7901 cells in the four groups: NC siRNA, NC siRNA+SDF-1, CXCR7 siRNA and CXCR7 siRNA+SDF-1. RESULTS: CXCR7 was expressed in the five gastric cancer cell lines, with the highest intensity in SGC-7901. The migrated and invasive cells increased in the NC siRNA+SDF-1 group and reduced in the CXCR7-siRNA group compared with the NC siRNA group (P<0.05). The CXCR7-siRNA+SDF-1 group had less migrated and invasive cells than the NC siRNA+SDF-1 group (P<0.05). CONCLUSIONS: CXCR7 is highly expressed in SGC-7901. SDF-1 promotes the migratory and invasive capability of SGC-7901 cells, but such an effect can be inhibited by silencing it with CXCR7siRNA.

[Effect of Chlorogenic Acid on Hepatic Stellate Cell Proliferation, Generation and Degradation of Extracelluar Matrix].

OBJECTIVE: To investigate the effects of chlorogenic acid (CGA) on hepatic stellate cell proliferation and the expression and secretion of Collagen I, Collagen III, tissue inhibitors of metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-2 (MMP-2). METHODS: An immortalized rat hepatic stellate cell (HSC) line was cultured in vitro. The cells were divided into 5 groups: control group; platelet-derived growth factor (PDGF) (10 ng/mL), PDGF+CGA (12.5 µg/mL), PDGF+CGA (25 µg/mL), PDGF+CGA (50 µg/mL) and CGA (50 µg/mL) group. After 24 hours treatment, the proliferation of HSC was detected by MTT method. The mRNA expression of Collagen I, Collagen III, TIMP-1 and MMP-2 were detected by RT-PCR. The protein levels of Collagen I, Collagen III, TIMP-1 and MMP-2 in the culture supernatant of HSC were measured by ELISA. RESULTS: PDGF increased the hepatic stellate cell proliferation, the mRNA expression and the protein levels of Collagen I, Collagen III and TIMP-1. (P < 0.05), which were significantly decreased by CGA (P < 0. 05). However, CGA had no significant influence on the expression of MMP-2. CONCLUSION: The antifibrotic effect of CGA may be related with the inhibition of hepatic stellate cell proliferation and generation of extracelluar matrix and promotion of extracelluar matrix degradation.

Decreased expression of gastrokine 1 in gastric mucosa of gastric cancer patients.

AIM: To investigate the expression of gastrokine 1 (GKN1) in normal gastric mucosa, precancerous lesions and gastric cancer tissues, and to analyse its correlations with tumour site and pathological pattern. METHODS: Thirty gastric cancer patients (12 cases of diffuse type and 18 cases of intestinal type), 13 atrophic gastritis patients and 15 healthy volunteers with almost normal gastric mucosa (superficial gastritis) were enrolled in this study. Helicobacter pylori (H. pylori) infection was examined in all subjects. All gastric mucosa biopsy specimens were obtained. Cancer-adjacent specimens were taken from corresponding gastric cancer patients. Immunohistochemistry and real-time PCR were performed to determine the expressions of the GKN1 protein and mRNA, respectively. RESULTS: H. pylori infection had no significant association with age, gender, tumour site or pathological pattern in all subjects. Compared with the superficial gastritis and atrophic gastritis groups, the expression of GKN1 protein (P = 0.011) and mRNA (P < 0.001) in gastric cancer was significantly decreased. The GKN1 mRNA level in diffuse type gastric cancer was significantly lower than in intestinal type gastric cancer (0.296 ± 0.076 vs 0.525 ± 0.164, P < 0.001). CONCLUSION: Compared with almost normal gastric mucosa, GKN1 expression in the gastric mucosa of gastric cancer patients is decreased; this is associated with progression and prognosis of gastric cancer.