Analysis of Threshold Change of Tumor Mutation Burden in Gastric Cancer.

BACKGROUND: The purpose of this study was to investigate the change of tumor mutation burden (TMB) in gastric cancer (GC) and its relationship with prognosis. METHODS: A total of 262 patients with GC from January 2018 to December 2019 were included in this study. All patients were in the advanced stage and were treated with surgical removal of D2 lymph nodes and dissection. Clinical data and gene expression profile data of the GC dataset in The Cancer Genome Atlas were collected. Patients were randomly divided into a high-level group and a low-level group according to the TMB of 8 mutations/Mb. TMB of GC was calculated based on cell mutation data. Cox regression model was used to evaluate the relationship between TMB and prognosis of GC patients. RESULTS: The total mutation rate of 262GC patients was 92.85%. The top 5 mutant genes were TP53, RB1, ARID1A, KMT2B, and RET. The expression level of TMB in GC patients was statistically significant with age, drinking history, and differentiation type. 94 of the 262 patients died, and 168 survived during the follow-up period. Patients with a high level of TMB had a worse prognosis than those with low level of TMB. The results of univariate and multivariate logistic analysis showed that the overall survival rate of GC patients was statistically significant with age, drinking history, clinical stage, differentiation type, and TMB. CONCLUSION: GC patients are often accompanied by changes in TMB, and its expression level is closely related to the degree of pathological differentiation, which is an independent factor affecting the prognosis of GC patients. High TMB value can evaluate the prognosis and provide a reference for the formulation of clinical treatment plans for GC patients.

Nomograms to Predict Overall and Cancer-Specific Survival in Gastric Signet-Ring Cell Carcinoma.

BACKGROUND: The objective of our study was to develop and validate nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with signet-ring cell carcinoma (SRCC) of the stomach. METHODS: Data were collected from the Surveillance, Epidemiology, and End Results (SEER) database. A total of 1781 patients were randomly allocated to a training set (n = 1335) and a validation set (n = 446). Univariate and multivariate analyses were used to determine the prognostic effect of variables. Nomograms were developed to estimate OS and CSS and assessed using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC), and decision curve analyses (DCA). DCA was utilized to compare the nomograms and the Tumor-Node-Metastasis (TNM) staging system. RESULTS: Age, race, tumor size, T, N, M stage, and use of surgery and/or radiotherapy were included in the nomograms. C-indexes for OS and CSS were 0.74 and 0.75 in the training set, respectively. C-indexes for OS and CSS were 0.76 and 0.76 in the validation set. Calibration plots and receiver operating characteristic (ROC) curves showed good predictive accuracy. According to the decision curve analyses (DCA), the new model was more useful than the TNM staging system. CONCLUSIONS: We developed nomograms to predict OS and CSS in patients with SRCC of the stomach. Nomograms may be a valuable clinical supplement of the conventional TNM staging system.

Medium-term follow-up of laparoscopic surgery on radical gastrectomy with D2 dissection for gastric cancer / 中国内镜杂志

Objective To explore the feasibility and clinical outcome of laparoscopy-assisted gastrectomy with D2 dissection by comparing the efficacy of open surgery on radical gastrectomy with D2 dissection for gastric cancer patients. Methods The patients with gastric cancer from October 2008 to August 2013 were divided into two groups according to the different surgical methods. Among them, 175 patients underwent laparoscopic surgery (laparoscopy-assisted surgery group, Group L), and 163 patients underwent laparotomy surgery (open surgery group, Group O). The number of lymph nodes dissected, postoperative recovery, complications, mortality and survival rate of the two groups were compared and analyzed. Results There was no significant difference in the number of lymph nodes resect between the two groups [Group L and Group O: (26.3 ± 13.9) vs (26.8 ± 10.2), t = -0.40, P = 0.684]. Compared with open surgery, the laparoscopy-assisted surgery showed significantly less intraoperative blood loss and quicker recovery of gastrointestinal function. The postoperative hospitalization time of laparoscopic group was less than that of laparotomy group, the difference was statistically significant (P < 0.05). No significant difference was found in 3-year survival rate between the two groups (Group L vs Group O: 92.00％ vs 92.63％, P = 0.262). Conclusions Compared to open surgery, laparoscopic gastrectomy is safer and has quicker postoperative recovery. There is no statistical difference in the number of resect lymph nodes between lapamscopic and open gastrectomy.

Lysine-specific demethylase 1 expression in zebrafish during the early stages of neuronal development.

Lysine-specific demethylase 1 (Lsd1) is associated with transcriptional coregulation via the modulation of histone methylation. The expression pattern and function of zebrafish Lsd1 has not, however, been studied. Here, we describe the pattern of zebrafish Lsd1 expression during different development stages. In the zebrafish embryo, lsd1 mRNA was present during the early cleavage stage, indicating that maternally derived Lsd1 protein is involved in embryonic patterning. During embryogenesis from 0 to 48 hours post-fertilization (hpf), the expression of lsd1 mRNA in the embryo was ubiquitous before 12 hpf and then became restricted to the anterior of the embryo (particularly in the brain) from 24 hpf to 72 hpf. Inhibition of Lsd1 activity (by exposure to tranylcypromine) or knockdown of lsd1 expression (by morpholino antisense oligonucleotide injection) led to the loss of cells in the brain and to a dramatic downregulation of neural genes, including gad65, gad75, and reelin, but not hey1. These findings indicate an important role of Lsd1 during nervous system development in zebrafish.

Ubiquitination of heat shock protein 27 is mediated by its interaction with Smad ubiquitination regulatory factor 2 in A549 cells.

Smad ubiquitination regulatory factor 2 (Smurf2) is a crucial part of the ubiquitin-proteasome pathway (UPP) that regulates cellular signal transduction via ubiquitin-dependent degradation of some substrates and receptors. The biological function of Smurf2 in lung diseases, however, is not clear. In this study, the authors found that overexpression of Smurf2 altered the subcellular localization and distribution of heat shock protein 27 (HSP27), and induced a decrease of HSP27 protein levels through HSP27 degradation by the UPP in human lung adenocarcinoma epithelial cell line A549. Colocalized assay using confocal microscopy and coimmunoprecipitated reciprocally by either antibody indicated the interaction between Smurf2 and HSP27, which suggested that Smurf2 mediated ubiquitylation-dependent degradation of HSP27 through their interaction in A549 cells.

[Clinical analysis of 67 patients with faces and jaws tumors].

OBJECTIVE: To explore the clinical features and the treatment result of occlusal surface bone tumors. METHOD: Sixty-seven patients with occlusal surface bone tumors were retrospective analyzed. RESULT: Benign and malignant tumors were respectively 57 (85%) and 10 (15%). Significant differences (P < 0.05) were observed between the age of male and female. Fifty-five patients followed up from 8 months to 10 years, fifteen patients closed to follow up. Five cases were found local recurrence of tumors in 52 patients. Fifteen patients were performed partial resection of mandible, among of them, 12 mandible defects were reconstructed simultaneously and the reconstruction, survived well without failure. CONCLUSION: Polycystic disease of the jaw are usually handled by curettage; Auto-bone transplantation is still a good method in the reconstruction of mandible defects.