Bioelectrical impedance analysis (BIA)-derived water composition ratios are non-invasive and cost-effective indices that reflect body fluid distribution. This study aimed to investigate the associations between these BIA-derived ratios and overall survival (OS) in patients with gastric cancer. A retrospective multicentre study included 385 gastric cancer patients. Optimal cut-offs were determined via receiver operating characteristic curves. Kaplan-Meier survival analysis, Cox regression analysis and restricted cubic spline (RCS) evaluated associations with OS. The optimal cut-off values were 0.389 for extracellular water (ECW)/total body water (TBW), 0·611 for intracellular water (ICW]/TBW and 0·638 for ECW/ICW. Kaplan-Meier survival analysis revealed that elevated ECW/TBW (72·6% vs. 58·7%; P < 0·001) and ECW/ICW (59·1% vs. 72·4%; P < 0·001) were associated with poorer OS, while a higher ICW/TBW (73·4% vs. 57·3%; P < 0·001) indicated better prognosis. In RCS models, ECW/TBW (hazard ratio (HR) = 1·552, 1·202-2·005, P = 0·001) and ECW/ICW (HR = 1·735, 1·320-2·280, P < 0·001) independently predicted worse OS, whereas ICW/TBW inversely correlated with mortality (HR = 0·620, 0·486-0·790, P < 0·001). Multivariable Cox regression analysis further confirmed that higher ECW/TBW (HR =1·552, 95% CI 1·272-2·688, P < 0·001) and ECW/ICW (HR = 1·735, 1·320-2·280, P < 0·001) ratios independently predicted worse OS. Conversely, a higher ICW/TBW ratio was inversely correlated with mortality (HR = 0·567, 95% CI 0·390-0·824, P = 0·003). The ECW/ICW ratio demonstrated the highest C-index (0·596), outperforming other ratios in predicting survival. These associations were consistent across subgroups, including advanced-stage patients. BIA-derived water composition ratios, particularly ECW/ICW, are robust and independent predictors of survival in gastric cancer patients, reflecting underlying metabolic and inflammatory disturbances. These non-invasive and cost-effective markers could enhance prognostic accuracy and guide personalised treatment strategies.

Background:Robotic total gastrectomy (RTG) has been proposed as a promising alternative to laparoscopic total gastrectomy (LTG) for advanced middle-upper gastric cancer (AMUGC) due to its potential to overcome anatomical challenges. However, the comparative evidence regarding both safety and long-term oncologic efficacy remains limited. Methods:This retrospective cohort study included 1099 patients with AMUGC who underwent RTG/LTG at eight high-volume centers in China between 2015 and 2019. Propensity score matching (PSM = 1:1) was used to balance clinicopathological characteristics between the two groups. The primary outcome was 3-year disease-free survival (DFS); secondary outcomes included 3-year overall survival (OS), 3-year cumulative incidence of recurrence (CIR), recurrence patterns, and operative outcomes. Results:In the PSM cohort, 229 patients were included in each group. RTG demonstrated lower overall postoperative complications (16.2% vs. 27.1%, P < 0.05), medical complications (6.6% vs. 17.0%, P < 0.05), and pneumonia rates (6.6% vs. 16.2%, P < 0.05). No differences were observed in 3-year DFS (73.7% vs. 68.1%, P = 0.230), 3-year OS (76.8% vs. 72.4%, P = 0.326), CIR (24.4% vs. 26.8%, P = 0.580), and recurrence patterns. In stage III, 3-year DFS was higher in the RTG group (67.4% vs. 54.5%, P = 0.047), but no significant differences were found in 3-year OS or CIR (all P > 0.05). Multivariate analysis confirmed that the surgical method was not significantly associated with 3-year DFS [hazard ratio (HR), 0.767; 95% confidence interval (CI), 0.542-1.086; P = 0.135] or 3-year OS (HR, 0.774; 95% CI, 0.534-1.122; P = 0.177). Conclusions:For AMUGC patients not receiving neoadjuvant chemotherapy, RTG demonstrated potential advantages in certain operative outcomes and non-inferior 3-year oncological outcomes compared with LTG. Prospective trials are needed to validate these findings.

Gastric cancer, a leading cause of cancer-related mortality globally, lacks robust biomarkers for comprehensive prognosis. Accordingly, we examined the prognostic utility of combining the albumin-prealbumin-globulin ratio (APGR) with mid-arm circumference (MAC) for assessing survival, malnutrition, and metastasis in gastric cancer. A multicenter cohort comprising 1,803 patients with gastric cancer was categorized into three groups based on APGR and MAC values: normal, moderate-risk, and high-risk grades. Associations with overall survival (OS), malnutrition, and metastasis were evaluated using Cox proportional hazard regression and logistic regression analyses. Normal grade patients exhibited the highest OS (68.6%), followed by those with medium-risk (53.9%) and high-risk (39.9%) grades (P < 0.001). Normal grade individuals had a 50% lower mortality risk (Hazard ratio [HR], 0.500, 95% confidence interval [CI]: 0.411-0.609; P < 0.001) than high-risk grade patients, with moderate-risk grade patients demonstrating a 27.2% reduction (HR, 0.728, 95% CI: 0.617-0.860; P < 0.001). Normal grade independently predicted a reduced risk of malnutrition (Odds ratio [OR], 0.249, 95% CI: 0.188-0.329; P < 0.001) and lower odds of metastasis (OR, 0.477, 95% CI: 0.324-0.701; P < 0.001). The composite index exhibited better discriminative ability (C-index = 0.595) than APGR (0.572) and MAC (0.558). Subgroup analyses revealed excellent prognostic discriminative ability across all TNM stages and sex subgroups, with sensitivity analysis, excluding early mortality, confirming the robustness of these findings. By integrating serological and anthropometric parameters, this composite index offers a clinically actionable framework for risk stratification in gastric cancer, improving the prognostic accuracy for survival, malnutrition, and metastasis. Its adoption can guide personalized interventions and improve clinical outcomes.

BACKGROUND:While robotic gastrectomy (RG) is increasingly used in gastric cancer surgery, its potential advantages over laparoscopic gastrectomy (LG) in intraoperative technical complexity (ITC) cases remain debated. METHODS:This retrospective cohort study included 3534 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals. ITC was defined by any of the following criteria: operative time exceeding the third quartile, intraoperative estimated blood loss ≥400 mL, or conversion to open surgery. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were conducted to compare short- and long-term outcomes. RESULTS:Patients with ITC comprised 25.9% (916/3534) of the cohort (RG: 260, LG: 656). After baseline adjustment, RG and LG groups were comparable in both PSM and IPTW cohorts. RG showed lower overall postoperative complications (11.5% vs. 20.1%, P = 0.003), particularly pneumonia (2.3% vs. 11.0%, P < 0.001) and shorter postoperative hospital stay (9.33 ± 4.41 vs. 10.77 ± 5.91 days, P < 0.001) compared to LG. These differences remained significant after PSM and IPTW analysis. The 3-year overall survival (83% vs. 78.8%, P = 0.15), disease-free survival (81.9% vs. 76.2%, P = 0.073), and cumulative recurrence risk (16.9% vs. 20%, P = 0.26) were comparable between RG and LG groups, consistent after PSM and IPTW. Multivariate analysis indicated that the surgical approach was not an independent factor influencing technical complexity. CONCLUSIONS:For patients with ITC, RG demonstrated superior short-term and comparable long-term outcomes than LG.

The comparative efficacy of robotic (RG) and laparoscopic gastrectomy (LG) in patients with gastric cancer with a body mass index (BMI) ≥ 25 kg/m2 remains unclear. We compared the outcomes between RG and LG in this patient population. This multicenter cohort study included 695 patients with gastric cancer with BMI ≥ 25 kg/m2 who underwent RG (n = 220) or LG (n = 475) at eight high-volume teaching hospitals in China. To reduce intergroup differences, overlap weighting (OW) and inverse probability of treatment weighting (IPTW) were applied. The primary end-points were short-term outcomes, 3-year survival, and recurrence. After OW and IPTW adjustments, the two groups’ baseline characteristics were well-balanced. Intraoperative blood loss, major bleeding rates, number of perioperative transfusions, and incidence of medical complications were lower, while operative time and costs were greater in the RG than LG group (all P < 0.05). Postoperative pneumonia rates tended to be lower in the RG group. The 3-year disease-free survival (DFS) or overall survival (OS) were comparable between groups. Subgroup analyses revealed no statistically significant interactions between the surgical approach and DFS or OS across all variables (all interactions, P > 0.05). Recurrence rates and patterns were comparable between the groups (all P > 0.05). For patients with gastric cancer with BMI ≥ 25 kg/m2, RG offers superior short-term outcomes compared to LG, while demonstrating non-inferior 3-year oncological outcomes. RG is a safe and effective surgical approach for managing gastric cancer in patients with elevated BMI.

There is limited evidence from large-scale multicenter studies regarding the short- and long-term efficacy of robotic gastrectomy (RG) in elderly patients diagnosed with gastric cancer (GC). As such, this retrospective investigation compared short-term outcomes and long-term oncological prognoses of RG versus (vs.) laparoscopic gastrectomy (LG) in a representative sample of this population. Data from 1393 patients ≥ 65 years of age diagnosed with GC, who underwent radical gastrectomy at 8 large tertiary hospitals in China between August 2016 and June 2019, were analyzed. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to reduce confounding bias. After IPTW and PSM adjustments, baseline characteristics between the RG and LG groups were comparable (standardized mean difference < 0.10). After IPTW adjustment, mean blood loss in the RG group was significantly less than that in the LG group (89.36 vs. 103.39 mL; p = 0.046) as was mean length of hospital stay (9.62 vs. 10.47 days; p = 0.017). There were no statistical differences in postoperative complications between the RG and LG groups (p > 0.05), nor in 3y-DFS (IPTW-adjusted: 74.5

BACKGROUND:To compare short-term and mid-term outcomes of robotic gastrectomy (RG) versus laparoscopic gastrectomy (LG) in high-risk gastric cancer (GC) patients. METHODS:Patients with ≥1 of the following criteria were defined as high-risk: age ≥80 years; BMI ≥30 kg/m2; ASA grade ≥ III; and clinical T stage (cT4). Finally, 2001 patients who underwent radical gastrectomy between August 2016 and June 2019 at eight high-volume hospitals were included and underwent 1:1 propensity score matching (PSM) with 534 patients in each group. RESULTS:After PSM, the RG group experienced less intraoperative blood loss (111.35 vs. 132.46 ml; P < 0.001) and a lower incidence of intraoperative massive haemorrhage (2.81 % vs. 5.62 %;P = 0.022), postoperative grade I-II complications (9.93 % vs.13.86 %; P = 0.047), medical complications (3.93 % vs. 8.61 %; P = 0.002), pneumonia (3.37 % vs. 7.30 %; P = 0.004), and pleural effusion (0.00 % vs. 0.75 %; P = 0.045) than the LG group. However, RG were associated with longer operative time (225.13 vs 210.51 min, P < 0.001) and significantly higher costs ($11,990 vs $8,040, P < 0.001). The three-year cumulative mortality rate (RG: 18.74 % vs. LG: 21.54 %, P = 0.280) and 3-year disease-free survival rate (RG: 78.97 % vs. LG: 75.45 %, P = 0.220) exhibited no statistically significant differences between surgical approaches. The 3-year overall recurrence rate was not significantly different between the RG and LG groups (22.47 % vs. 19.66 %; P = 0.294). CONCLUSIONS:RG yielded better short-term outcomes and comparable mid-term prognoses than LG for patients with high-risk resectable gastric cancer.

Patient reported outcomes is currently considered to be an important supplement to evaluate the effectiveness of enhanced recovery after surgery (ERAS) clinical practice. The Quality of Recovery-40 Questionnaire (QoR-40) is one of the most frequently used and validation tool to assess the subjective feelings of quality of life after surgery. The present study aimed to use the QoR-40 to evaluate the effectiveness of ERAS protocols in gastric cancer from the perspective of patient-reported quality of recovery. The study was designed as a prospective, non-randomized clinical trial, conducted in a single center. Patients in our hospital who were scheduled to undergo radical surgery for gastric cancer were divided into ERAS group and control group (Contr group). The QoR-40 were administered one day before surgery (Baseline) and on postoperative day 1, 3, 6, and 30. The difference in QoR-40 scores between the ERAS and Contr groups was compared by repeated-measures ANOVA. A total of 200 patients completed the study, including 100 patients in the ERAS group and 100 patients in the Contr group. The Baseline time point QoR-40 scores of the ERAS and Contr groups were 179.68 ± 14.46 and 180.12 ± 17.12, respectively, and no significant difference was noted between the two groups (p = 0.845). The postoperative QoR-40 score of the ERAS group was significantly higher than that of the Contr group, and the difference was statistically significant (p = 0.006). This study demonstrated that, in terms of patient-reported quality of recovery, the postoperative recovery effect of ERAS protocols in gastric cancer is significantly better than that of the traditional treatment model.

Objective: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. Background: The clinical outcomes of RG over LG have not yet been effectively demonstrated. Methods: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). Results: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% (P=0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively (P=0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P=0.988). There was no significant difference in the recurrence sites between the 2 groups (all P>0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P=0.745) and overall survival (79.7% vs 78.4%, P=0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P>0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P>0.05). Conclusions: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.

BackgroundRecent studies have reported hypersensitive C-reactive protein (hs-CRP) linked to clinicopathological characteristics and nutritional status of the tumor, but its clinical significance in GC remains unclear. This study aimed to investigate the relationship between preoperative serum hs-CRP level and clinicopathological features and nutritional status in gastric cancer (GC) patients.MethodsThe clinical data of 628 GC patients who met the study criteria were analyzed retrospectively. The preoperative serum hs-CRP level was divided into two groups (<1 mg/L and ≥1 mg/L) to evaluate clinical indicators. Nutritional Risk Screening and nutritional assessment of GC patients were performed by the Nutritional Risk Screening 2002 (NRS2002) and the Patient-Generated Subjective Global Assessment (PG-SGA), respectively. The data were subjected to chi-square test, univariate and multivariate logistic regression analyses, respectively.ResultsThe analysis of 628 GC cases revealed that 338 patients (53.8%) were on malnutrition risk(NRS2002≥3 points), and 526(83.8%) had suspected/moderate to severe malnutrition(PG-SGA≥ 2 points). Preoperative serum hs-CRP level was significantly correlated with age, tumor maximum diameter (TMD), peripheral nerve invasion (PNI), lymph-vascular invasion (LVI), depth of tumor invasion (DTI), lymph node metastasis (LNM), pTNM stage, body weight loss (BWL), body mass index (BMI), NRS2002 score, PG-SGA grade, hemoglobin (HB), total protein (TP), albumin (ALB), prealbumin (PAB) and total lymphocyte count (TLC). Multivariate logistic regression analysis revealed that hs-CRP (OR=1.814, 95%CI=1.174-2.803; P=0.007), age, ALB, BMI, BWL and TMD were independent risk factors for existing malnutritional risk in GC. Similarly, non-malnutrition and suspected/moderate to severe malnutrition groups presented that hs-CRP (OR=3.346, 95%CI=1.833-6.122; P< 0.001), age, HB, ALB, BMI and BWL were independent risk factors for malnutrition in GC.ConclusionIn addition to the generally used nutritional evaluation indicators such as age, ALB, BMI, and BWL, the hs-CRP level may be used as a nutritional screening and evaluation indicator for GC patients.

Background Accumulating evidence indicates that type II cystatin (CST) genes play a pivotal role in several tumor pathological processes, thereby affecting all stages of tumorigenesis and tumor development. However, the prognostic and predictive value of type II CST genes in GC has not yet been investigated. Methods The present study evaluated the expression and prognostic value of type II CST genes in GC by using The Cancer Genome Atlas (TCGA) database and the Kaplan–Meier plotter (KM plotter) online database. The type II CST genes related to the prognosis of GC were then screened out. We then validated the expression and prognostic value of these genes by immunohistochemistry. We also used Database for Annotation, Visualization, and Integrated Discovery (DAVID), Gene Multiple Association Network Integration Algorithm (GeneMANIA), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), nomogram, genome-wide co-expression analysis, and other bioinformatics tools to analyze the value of type II CST genes in GC and the underlying mechanism. Results The data from the TCGA database and the KM plotter online database showed that high expression of CST2 and CST4 was associated with the overall survival (OS) of patients with GC. The immunohistochemical expression analysis showed that patients with high expression of CST4 in GC tissues have a shorter OS than those with low expression of CST4 (HR = 1.85,95%CI: 1.13–3.03, P = 0.015). Multivariate Cox regression analysis confirmed that the high expression level of CST4 was an independent prognostic risk factor for OS. Conclusions Our findings suggest that CST4 could serve as a tumor marker that affects the prognosis of GC and could be considered as a potential therapeutic target for GC.

Gastric cancer (GC) is a heterogeneous disease with poor prognosis. Tumor-derived extracellular vesicles (EVs) assume a role in intercellular communication by carrying various molecules, including proteins, RNA, and DNAs, which has been identified to exhibit oncogenic effect in GC. Therefore, this research aimed to figure out whether tumor-derived EVs transmit c-Myc to orchestrate the growth and metastasis of GC. KCNQ1OT1, microRNA (miR)-556-3p and CLIC1 expression of GC tissues was detected through RT-qPCR. EVs were isolated from GC cells, followed by RT-qPCR and Western blot analysis of c-Myc expression in EVs and GC cells. Next, GC cells were incubated with EVs or transfected with a series of mimic, inhibitor, or siRNAs to assess their effects on cell viability, migrative, invasive, and apoptotic potential. Relationship among c-Myc, KCNQ1OT1, miR-556-3p, and CLIC1 was evaluated by dual-luciferase reporter assay. PI3K/AKT pathway-related proteins were assessed through Western blot analysis. KCNQ1OT1 and CLIC1 were highly expressed but miR-556-3p in GC tissues. c-Myc was high-expressed in tumor-derived EVs and GC cells. Mechanistically, c-Myc could induce KCNQ1OT1 expression, and KCNQ1OT1 bound to miR-556-3p that negatively targeted CLIC1 to inactivate PI3K/AKT pathway. Tumor-derived EVs, EVs-c-Myc, KCNQ1OT1 or CLIC1 overexpression, or miR-556-3p inhibition promoted GC cell proliferative, invasive, and migrative capacities but repressed their apoptosis through activating PI3K/AKT pathway. Collectively, tumor-derived EVs carrying c-Myc activated KCNQ1OT1 to downregulate miR-556-3p, thus elevating CLIC1 expression to activate the PI3K/AKT pathway, which facilitated the growth and metastasis of GC.

BackgroundAnalyses in silico suggested the upregulation of a circular RNA (circRNA), circ_0008287, in gastric cancer and possible interactions among microRNA (miR)-548c-3p, circ_0008287, and intracellular chloride channel protein 1 (CLIC1). This study aims to testify whether circ_0008287 can affect the immune escape of gastric cancer cells by regulating miR-548c-3p and CLIC1.MethodsRT-qPCR was performed to determine the expression pattern of circ_0008287 in gastric cancer cells. Gain- and loss-of function assays were then performed to assess the effects of circ_0008287 on malignant phenotypes of cancer cells. Interactions among circ_0008287, miR-548c-3p and CLIC1 were verified by dual luciferase reporter gene, RIP and FISH assays. Effects of CLIC1 on IFN-γ secretion and apoptosis in CD8 + T cells were evaluated by flow cytometry following co-culture of CD8 + T cells with cancer cells overexpressing/silencing CLIC1. A gastric cancer mouse model was further developed for in vivo investigation on effects of circ_0008287 on tumorigenesis and tumor metastasis.Resultscirc_0008287, an upregulated circRNA in gastric cancer cells, augmented the viability as well as invasive and migratory potentials of gastric cancer cells. By competitively binding to miR-548c-3, circ_0008287 increased the expression of CLIC1, which impaired the function of CD8 + T cells and promoted their apoptosis. After downregulation of circ_0008287, in vivo tumorigenesis and metastasis were suppressed.ConclusionHence, this study suggests the promotive role of circ_0008287 in gastric cancer progression and immune escape and further elucidates the underlying circ_0008287/miR-548c-3p/CLIC1 regulatory axis.

Background. ITGA5 is an adhesion molecule that integrates the intracellular structures with the extracellular matrix to perform biological functions. However, ITGA5 is highly expressed in a variety of tumors and is involved in tumor progression by promoting cell proliferation and metastasis. Nevertheless, little research has been performed on its function in gastric cancer. Therefore, the aim of this study was to investigate the role of ITGA5 in gastric cancer, focusing on the mechanism regulating the proliferation, invasion and migration. Methods. The expression of ITGA5 in gastric cancer tissues was assessed by the use of molecular bioinformatics databases and high-throughput sequencing of gastric cancer tissues from patients. Western blot, qPCR, and immunohistochemistry were performed to detect the expression of ITGA5 in samples from gastric cancer patients and gastric cancer cell lines. Furthermore, the ITGA5 gene was silenced and overexpressed in gastric cancer cells, and the effect on proliferation, invasion, migration, and tumorigenic ability was assessed. Results. ITGA5 mRNA and protein expression were upregulated in gastric cancer cell lines and tissues from patients, and its expression was closely associated with tumor size, lymph node metastasis, and TNM stage. In vitro and in vivo experiments showed that ITGA5 silencing resulted in the inhibition of proliferation, invasion, migration, and graft growth of gastric cancer cells; conversely, the overexpression resulted in the promotion of these cell functions. Our results finally showed that the effect of ITGA5 on proliferation, invasion, and migration of gastric cancer cells was performed through the activation of the FAK/AKT pathway. Conclusions. ITGA5 promotes proliferation, invasion, and migration of gastric cancer cells through the activation of FAK/AKT signaling pathway, suggesting that ITGA5 may be potentially considered as a new target in gastric cancer therapy.

Aims: This study aimed to explore the function of NKCC1 in the proliferation, migration and invasion of Gastric cancer (GC) cells.Materials and Methods: GC data extracted from the database was analyzed using molecular bioinformatics. The expression levels of NKCC1 in tissue samples from GC patients and GC cell lines were determined by Western blotting, qRT-PCR, and immunohistochemistry. Immunofluorescence was used to detect protein localization. The GC cell lines were transfected with NKCC1-shRNA or expression plasmid, and in vitro proliferation, invasion and migration were analyzed by the CCK8, wound healing and transwell tests.Results: The NKCC1 mRNA level was significantly increased in GC tissues than that in normal gastric tissues (P = 0.0195). This phenomenon was further confirmed by the analysis of the TCGA-GTEx database that includes 408 gastric cancer tissues and 211 normal gastric tissues (P < 0.01). Furthermore, the increased level of NKCC1 was significantly correlated with Tumor size (P = 0.039), lymphatic node metastasis (P = 0.035) and tumor stage (P = 0.034). In vitro experiments confirmed that NKCC1 expression was higher in GC cells compared to that in GES-1 cells, and was mainly localized to the cytoplasm and membrane. NKCC1 silencing inhibited GC cell proliferation, invasion, migration and EMT, whereas its overexpression had the opposite effects. Furthermore, NKCC1 overexpression upregulated and activated JNK, and the targeted inhibition of JNK by SP600125 abrogated the pro-metastatic effects of NKCC1.Conclusions: NKCC1 promotes migration and invasion of GC cells by MAPK-JNK/EMT pathway and can be a potential therapeutic target.

α-Actinin1 (ACTN1), an actin cross-linking protein, is implicated in cytokinesis, cell adhesion, and cell migration. In addition, it is involved in the tumorigenesis and development of certain cancers, such as breast cancer. We explored the function of ACTN1 in gastric cancer (GC), which has largely remained unclear. High-throughput sequencing and public microarray datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) revealed the upregulation of ACTN1 in gastric cancer with a poor prognosis. These results were further verified by western blotting (WB), Real-Time Quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry. We constructed loss and gain of function gastric cancer cells, which revealed the effect of ACTN1 over-expression on promoting GC cell proliferation, invasion, migration, and inhibited apoptosis. Mechanistic studies revealed that ACTN1 regulates the epithelial-mesenchymal transition (EMT) and tumorigenesis of gastric cancer via the AKT/GSK3β/β-catenin pathway, confirmed by the inhibitor of AKT MK2206. Altogether, these results demonstrated that ACTN1 could be a promising candidate for gastric cancer treatment.

Gastric cancer (GC) is one of the most frequently diagnosed gastrointestinal cancer types in the world. Novel prognostic biomarkers are required to predict the progression of GC. Glutathione S-transferase Mu (GSTM) belongs to a family of phase II enzymes that have been implicated in a number of cancer types. However, the prognostic value of the GSTM genes has not been previously investigated in GC. The Cancer Genome Atlas (TCGA) was used to evaluate mRNA expression levels of GSTMs in GC tissue samples. Overall survival (OS) rates, hazard ratios (HRs) and 95% CIs were calculated using the Cox logistic regression model and Kaplan-Meier (KM) analysis was performed. In addition, the KM plotter online database was used to validate mRNA expression and the prognostic value of GSMT family members in patients with GC. To predict the function of GSTM genes in these patients, several bioinformatics tools, including the Database for Annotation, Visualization and Integrated Discovery, gene multiple association network integration algorithm, Search Tool for the Retrieval of Interacting Genes/Proteins, Gene Set Enrichment Analysis (GSEA), nomogram and genome-wide co-expression analysis were used. In the present study, high expression of GSTM5 was indicated to be strongly associated with lower OS in patients with GC, according to the TCGA and KM plotter online databases (HR=1.47, 95% CI: 1.06-2.04, P=0.021; and HR=1.69, 95% CI: 1.42-2.01, P=1.6×10-9, respectively). The results from the GSEA and genome-wide co-expression analysis indicated that GSTM5 expression associated with several biological process terms, including 'adhesion', 'angiogenesis', 'apoptotic process', 'cell growth', 'proliferation', 'migration', 'Hedgehog signaling', 'MAPK signaling' and the 'TGF-β signaling pathway'. In conclusion, the present results indicated that GSTM5 may serve as a biomarker for GC prognosis and may be a potential therapeutic target for GC.

Background . Integrins are involved in the biological process of a variety of cancers, but their importance in the diagnosis and prognosis of gastric cancer (GC) is still unclear. Therefore, this study aimed at exploring the significance of ITG gene expression in GC to evaluate its diagnosis and prognosis. Methods . GEPIA data were used to evaluate the mRNA expression of ITG genes in GC patients. The prognostic value of these genes was assessed by analyzing their mRNA expression using the Kaplan–Meier curve. The biological function of ITG genes was evaluated by GC tissue sequencing combined with GSEA bioinformatics. Based on the sequencing data, ITGA5 with the largest expression difference was selected for verification, and RT-PCR was used to verify its mRNA expression level in 40 pairs of GC and normal tissues. Results . ITG (A2, A3, A4, A5, A6, A11, AE, AL, AM, AV, AX, B1, B2, B4, B5, B6, and B8) was highly expressed in GC tissues, while ITGA8 was low, compared with their expression in normal tissues. RNA-seq data shows that ITG (A2, A5, A11, AV, and B1) expression was associated with poor prognosis and overall survival. In addition, combined with the results of GC tissue mRNA sequencing, it was further found that the differentially expressed genes in the ITGs genes. ITGA5 was highly expressed in GC tissues compared with its expression in normal tissues, as evaluated by qRT–PCR ( P < 0.001) and ROC ( P < 0.001, AUC (95% CI) = 0.747 (0.641–0.851)), and confirmed that ITGA5 expression was a potential diagnostic marker for GC. Bioinformatics analysis revealed that the signaling pathway involved in ITGA5 was mainly enriched in focal adhesion, ECM-receptor interaction, and PI3K-AKT and was mainly involved in biological processes such as cell adhesion, extracellular matrix, and cell migration. Conclusion . This study suggested that ITGs were associated with the diagnosis and prognosis of GC and discovered the prognostic value and biological role of ITGA5 in GC. Thus, ITGA5 might be used as a potential diagnostic marker for GC.

Purpose: The present study aimed to develop the official Chinese version of the QoR-40 (QoR-40C) and to test its reliability, validity, and responsiveness. Patients and Methods: A systematic translation procedure was established and performed to develop the QoR-40C from the original English QoR-40 version. After the pilot study, 223 surgical patients were administered the QoR-40C at four time points. The validity, reliability, and responsiveness were assessed to validate the QoR-40C. Results: The test-retest reliability of the QoR-40C in the morning and afternoon of the third day after surgery was 0.917 (P < 0.001). The split-half reliability for all domains was 0.938 in the morning of the third day after surgery. The median item-to-own dimension and total score of Cronbach's alpha for internal consistency of the QoR-40C at different assessment time points were more than 0.70. All the correlation coefficients between each subscale and the QoR-40 total score showed good correlation and were greater than those for other subscales in the morning of the third day after surgery. Furthermore, in the morning of the third day after surgery, the QoR-40C total score was moderately positively correlated with the SF-36 score (rho = 0.575, P < 0.001), while the QoR-40C score was negatively correlated with the visual analogue scale (VAS) score (rho = -0.299, P < 0.001). The factor loadings of each item were within the required range. A statistically significant difference was observed in the QoR-40C total scores before and after the surgery (P < 0.001) with the standardized responsive mean (SW) of 0.51. Conclusion: The QoR-40C showed good reliability, validity, and responsiveness and was appropriate to be used as a quality of life measurement questionnaire for patients after surgery in China.

Objective To establish a cisplatin-resistant gastric cancer cell line MGC-803/cisplatin (DDP) and to explore its drug resistance mechanism.Methods The cisplatin was used to induce the drug resistance of MGC-803 cells.The half maximal inhibitory concentration (IC50) of the drug-resistant strains was detected by the cell counting kit-8 (CCK-8) method.The expression of chloride intracellular channel 1 (CLIC1) was detected by Western blotting analyses.The wild-type CLIC1 plasmid and the short hairpin RNA (shRNA) plasmid targeting CLIC1 were constructed.After Lipo3000 was transfected into gastric cancer cells,the IC50 of gastric cancer cells to cisplatin was detected,and then the intracellular Cl-concentration was detected by MQAE fluorescent probe.Results The cisplatin-resistant cell line MGC-803/DDP was successfully induced with an IC50 of (7.02 ± 0.13) mg/L,while the IC50 of MGC803 was (1.29 ± 0.09) mg/L,(t =36.090,P ＜ 0.05).The CLIC1 protein of MGC803/DDP was up-regulated by (2.27 ± 0.15) times relative to MGC803 (t =7.841,P ＜ 0.05).After silencing the CLIC1 gene of MGC803/DDP,the IC50 of the CON,CN,and KD groups were (6.96 ±0.09),(6.93 ± 0.15) and (3.02±0.20) mg/L,respectively,which was significantly decreased in the KD group (F =0.209,P ＜ 0.05).After overexpression of the CLIC1 gene in MGC803 cells,the IC50 of the CON,CN,and OE groups were (1.35 ±0.07),(1.25 ±0.07) and (4.77 ±0.12) mg/L,respectively,and the OE group was significantly elevated (F =0.508,P ＜ 0.05).The concentration of chloride ion was detected by MQAE.The relative fluorescence intensity of MGC-803,MGC-803/OE,MGC-803/DDP and MGC-803/DDP-KD were (1.02±0.03),(0.61±0.02),(0.67±0.01) and (1.39±0.02),respectively.The concentration of Cl-in MGC-803/OE cells was higher than that in MGC-803 (t =10.800,P ＜ 0.05),while the concentration of Cl-in MGC-803/DDP was higher than that in MGC-803 and MGC-803/DDP-KD,and the concentration of Cl-in KD group was the lowest (F =229,P ＜ 0.05).Conclusion The CLIC1 gene can induce the resistance of gastric cancer cell line MGC-803 to cisplatin in vitro.The mechanism may be related to the up-regulation of CLIC1 expression,which leads to an increase of intracellular chloride ion concentration.