High mobility group-box 3 overexpression is associated with poor prognosis of resected gastric adenocarcinoma

AIM:To elucidate high mobility group-box 3(HMGB3) protein expression in gastric adenocarcinoma,its potential prognostic relevance,and possible mechanism of action.METHODS:Ninety-two patients with gastric adenocarcinomas surgically removed entered the study.HMGB3 expression was determined by immunohistochemistry through a tissue microarray procedure.The clinicopathologic characteristics of all patients were recorded,and regular follow-up was made for all patients.The inter-relationship of HMGB3 expression with histological and clinical factors was analyzed using nonparametric tests.Survival analysis was carried out by Kaplan-Meier(log-rank) and multivariate Cox(Forward LR) analyses between the group with overexpression of HMGB3 and the group with low or no HMGB3 ex-pression to determine the prognosis value of HMGB3 expression on overall survival.Further,HMGB3 expression was knocked down by small hairpin RNAs(shRNAs) in the human gastric cancer cell line BGC823 to observe its influence on cell biological characteristics.The MTT method was utilized to detect gastric cancer cell proliferation changes,and cell cycle distribution was analyzed by flow cytometry.RESULTS:Among 92 patients with gastric adenocarcinomas surgically removed in this study,high HMGB3 protein expression was detected in the gastric adenocarcinoma tissues vs peritumoral tissues(P < 0.001).Further correlation analysis with patients' clinical and histology variables revealed that HMGB3 overexpression was obviously associated with extensive wall penetration(P = 0.005),a positive nodal status(P = 0.004),and advanced tumor-node-metastasis(TNM) stage(P = 0.001).But there was no correlation between HMGB3 overexpression and the age and gender of the patient,tumor localization or histologic grade.Statistical Kaplan-Meier survival analysis disclosed significant differences in overall survival between the HMGB3 overexpression group and the HMGB3 no or low expression group(P = 0.006).The expected overall survival time was 31.00 ± 3.773 mo(95%CI = 23.605-38.395) for patients with HMGB3 overexpression and 49.074 ± 3.648 mo(95%CI = 41.925-57.311) for patients with HMGB3 no and low-level expression.Additionally,older age(P = 0.040),extensive wall penetration(P = 0.008),positive lymph node metastasis(P = 0.005),and advanced TNM tumor stage(P = 0.007) showed negative correlation with overall survival.Multivariate Cox regression analysis indicated that HMGB3 overexpression was an independent variable with respect to age,gender,histologic grade,extent of wall penetration,lymph nodal metastasis,and TNM stage for patients with resectable gastric adenocarcinomas with poor prognosis(hazard ratio = 2.791,95%CI = 1.233-6.319,P = 0.019).In the gene function study,after HMGB3 was knocked down in the gastric cell line BGC823 by shRNA,the cell proliferation rate was reduced at 24 h,48 h and 72 h.Compared to BGC823 shRNA-negative control(NC) cells,the cell proliferation rate in cells that had HMGB3 shRNA transfected was significantly decreased(P < 0.01).Finally,cell cycle analysis by FACS showed that BGC823 cells that had HMGB3 knocked down were blocked in G1/G0 phase.The percentage of cells in G1/G0 phase in BGC823 cells with shRNA-NC and with shRNA-HMGB3 was 46.84% ± 1.7%,and 73.03% ± 3.51% respectively(P = 0.001),whereas G2/M cells percentage decreased from 26.51% ± 0.83% to 17.8% ± 2.26%.CONCLUSION:HMGB3 is likely to be a useful prognostic marker involved in gastric cancer disease onset and progression by regulating the cell cycle.

Short Term Operative Outcomes of Laparoscopic Gastric Mobilization in Esophagectomy for Esophageal Cancer: Comparison with Hand Assisted Technique

Objective: This study evaluated the safety and operative utilities of the laparoscopic gastric mobilization compared with hand-assisted laparoscopic gastric mobilization. Patients and Methods: From April 2010 to November 2015, 125 patients with esophageal cancer have been performed laparoscopic mobilization;33 under hand-assisted laparoscopic gastric mobilization (HLG group) and 92 under laparoscopic gastric mobilization without hand-assisted technique (LG group). Preoperative data and surgical outcomes of 2 groups were compared. Results: Preoperative data were not significantly different except for BMI. Operation time in abdominal procedure of LG group is significantly longer than HLG group (P < 0.0001). Otherwise, the blood loss and number of dissected nodes of abdominal procedure was not significantly different in two groups. The perioperative blood transfusions were needed in 7 cases (21.2%) in HLG group and 25 (27.1%) in LG group. The postoperative complications and mortality within 30 days after surgery were not significantly different in two groups. The length of hospital stay was 29 days in HLG group and 31 days in HG group, respectively. Conclusions: Our results suggested that laparoscopic gastric mobilization was safe technique and the short-term operative outcomes were comparable with that of hand-assisted laparoscopic mobilization.