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.

Prognostic analysis of prostaglandin D2 synthase in diffuse large B‑cell lymphoma

Purpose We aimed to analyse the correlation between prostaglandin D2 synthase(PTGDS)and a diffuse large B-cell lymphoma(DLBCL)prognosis.Methods We retrospectively collected two hundred paraffin-embedded tissue specimens that were pathologically diagnosed as DLBCL in the Fujian Tumour Hospital between January 2014 and December 2018.An abundance of paraffin-embedded tumour tissues were obtained.Twenty patients with lymphocyte-rich,benign,tissue-reactive,hypertrophic tonsillitis were selected as controls.Wax blocks were selected for primary cases and the controls were screened by professional pathologists.The levels of prostaglandin D2 synthase(PTGDS)and the EMT-related molecules,E-cadherin and vimentin,were detected by immunohistochemistry in clinical samples.A chi-square test revealed the correlations between PTGDS expression and clinicopathological characteristics,including age,sex,primary site,clinical stage,immunotyping,and International Prognostic Index(IPI)score.The Kaplan–Meier survival analysis was performed,and the diagnostic value was evaluated by receiver operating characteristic(ROC)curve analysis.Results A total of 138 cases(69%)were found to be PTGDS positive(>30%positive cells).PTGDS staining was negative(<30%positive cells)in 62 cases(31%).We collected the corresponding clinicopathological information and found that PTGDS expression was not significantly related to the patients’age,tumour stage,presence of extranodal invasion,or IPI score.According to the follow-up data,patients with low PTGDS expression had poor progression-free survival(PFS)and overall survival(OS),with 2-year PFS and OS rates of 41.7%and 50%,respectively.The 2-year PFS and OS rates of PTGDS-positive patients were 89.3%and 92.9%,respectively(P<0.0001),and the differences were significant.Conclusion We found that the expression level of PTGDS is significantly correlated with the prognosis of diffuse large B-cell lymphoma.

Prognostic value of clinical characteristics and immunophenotypic biomarkers in 115 patients with primary central nervous system lymphoma

Background Clinical outcome in patients with primary central nervous lymphoma （PCNSL） is variable and poorly predictable. This study investigated the association of clinical features and immune markers with prognosis of patients with PCNSL. Methods One hundred and fifteen newly diagnosed PCNSL patients at the study institution were considered eligible for this study. Clinical characteristics and biochemical assay data were collected. Immunohistochemical staining of Cyclin D3, Cyclin E, Foxpl, and LMO2 were performed. All cases were followed-up regularly. Results The common sites of involvement were frontal lobe （54.8%） and thalamus （16.5%）. Diffuse large B-cell lymphoma composed of 96.5% of the cases. The median overall survival was 22 （4-41） months, and the 5-year survival rate was 22.8%. Age 〉65 years, serum globulin 〉40 g/L, large size of tumor, lymphocyte count ≥1×10^9/L, and expression of Cyclin D3 and Cyclin E were associated with poor prognosis of PCNSL. Expressions of Foxpl, LMO2, and CD44 were not related to the survival. Expression of Cyclin E, large tumor size, and high serum globulin were independent prognostic factors for PCNSL. Conclusions PCNSL prognosis is relatively poor. Age, high tumor burden, higher lymphocyte count, expression of Cyclin D3, and Cyclin E are inferior prognostic factors for PCNSL.