To determine the chronology of oncogenes in gastric carcinogenesis, we studied oncoproteins of c-Ha/Ki/N-ras, c-erbB-2, and pan-myc in gastric malignant and premalignant lesions of Wistar rats induced by MNNG using im-munohistochemistry. c-ras p21 cytoplasmic staining was seen in 7/23 (30.4%) of gastric adenocarcinomas and found to correlate with the staging of lesions. c-erbB-2 p185 cellular membrance staining was observed in 17/33 (51.5%) and pan-myc p62, in 33/39 (84.6%) chronic atrophic gastritis. The highest positive rate of the concomitant expression of these genes was observed in adenocarcinomas (17.4%). Higher expression level of these three oncoproteins were found in the antral area than those in the fundic area, expression of the three oncogenes was found in adenocarcinomas (17.4%) (P

Objective: To study the association between the AKAP12 promoter methylation and recurrence of hepatocellular carcinoma. Methods: A total of 142 primary liver cancer patients underwent surgery in department of Hepatobiliary surgery in Peking University Cancer Hospital from 2003 to 2009 were selected as subjects in the survey; with the inclusion criteria as hepatocellular carcinoma, no cancer cells were observed in the surgical margin(SM) samples. All patients had neither lymph nor distant metastasis at the time of surgery, and receiving complete follow-up data for at least 3 years. By the end of May 2014, a total of 75 patients had relapsed of whom 71 died and there were no lost. All samples were acquired from the frozen surgical tissues. Genomic DNA was extracted using phenol/chloroform method and performed bisulfite modification following with polymerase chain reaction (PCR). AKAP12 methylation in hepatoma and the corresponding SM samples from 142 patients was determined by denature high-performance liquid chromatography (DHPLC) and bisulfite clone sequencing. Kaplan-Meier and Cox proportion hazard regression model were used to identify the factors related to the survival time. Results: In 142 cases, 125 patients (88.0%) were male and 17 (12.0%) cases were female. The median age was 52.5 years, ranging from 34 years to 76 years. AKAP12 methylation-positive rate was significantly higher in hepatomas than SMs (54.9% vs. 10.2%, P<0.001). Patients with AKAP12 methylation-positive had less risk of the recurrence (HR=0.62, 95%CI: 0.39-0.99); with tumor diameter more than 5 cm (HR=1.53, 95%CI: 1.00-2.50),portal vein invasion(HR=4.53, 95% CI:2.69-7.64) increased the recurrence risk. Moreover, portal vein invasion had a higher risk of death (HR=2.98, 95% CI: 1.73-4.98). Conclusion There was significant association between AKAP12 DNA methylation and low risk of recurrence and long progression-free survival of hepatocellular carcinoma patients.