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Purpose: To investigate the role of computed tomography (CT) radiomics for the preoperative prediction of lymph node (LN) metastasis in gastric cancer.Materials and Methods: This retrospective study included 247 consecutive patients (training cohort, 197 patients; test cohort, 50 patients) with surgically proven gastric cancer. Dedicated radiomics prototype software was used to segment lesions on preoperative arterial phase (AP) CT images and extract features. A radiomics model was constructed to predict the LN metastasis by using a random forest (RF) algorithm. Finally, a nomogram was built incorporating the radiomics scores and selected clinical predictors. Receiver operating characteristic (ROC) curves were used to validate the capability of the radiomics model and nomogram on both the training and test cohorts.Results: The radiomics model showed a favorable discriminatory ability in the training cohort with an area under the curve (AUC) of 0.844 (95% CI, 0.759 to 0.909), which was confirmed in the test cohort with an AUC of 0.837 (95% CI, 0.705 to 0.926). The nomogram consisted of radiomics scores and the CT-reported LN status showed excellent discrimination in the training and test cohorts with AUCs of 0.886 (95% CI, 0.808 to 0.941) and 0.881 (95% CI, 0.759 to 0.956), respectively.Conclusions: The CT-based radiomics nomogram holds promise for use as a noninvasive tool in the individual prediction of LN metastasis in gastric cancer.Key Points: • CT radiomics showed a favorable performance for the prediction of LN metastasis in gastric cancer. • Radiomics model outperformed the routine CT in predicting LN metastasis in gastric cancer. • The radiomics nomogram holds potential in the individualized prediction of LN metastasis in gastric cancer. [ABSTRACT FROM AUTHOR]

The effects of nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) on tumor cells and the relevant mechanisms are less well defined. This study aimed to explore the role and mechanism of action of NUCKS1 in gastric cancer (GC) progression. The expression dynamics of NUCKS1 were examined using microarray-based immunohistochemistry (IHC) in a group of carcinomatous and adjacent non-tumor specimens. Various in vitro and in vivo assays were performed to clarify the function of NUCKS1 in GC and its underlying mechanisms. In our research, NUCKS1 overexpression was identified by IHC in 86/200 (43%) GC patients, was significantly related to the invasive phenotype of GC and was an indisputable predictor of shortened survival. Depleting NUCKS1 in GC cells significantly induced apoptosis and reduced cell proliferation and invasiveness in vitro and inhibited tumor growth in vivo. Additionally, ectopic overexpression of NUCKS1 in GC cells enhanced proliferation and invasion in vitro and promoted tumor growth in vivo. Importantly, PI3K/Akt/mTOR signaling pathway activity was inhibited upon downregulation of NUCKS1 expression and enhanced by ectopic overexpression of NUCKS1. Subsequently, the insulin-like growth factor 1 receptor (IGF-1R) gene was found to be a potential downstream target of NUCKS1 in GC cells, and knockdown of IGF-1R eliminated the augmentation of GC cell migration, invasion and proliferation as well as PI3K/Akt/mTOR signaling pathway activity by ectopic NUCKS1. The data suggested that NUCKS1 enhanced GC aggressiveness via the PI3K/Akt/mTOR signaling pathway in an IGF-1R-dependent manner. NUCKS1 or its respective signaling pathways could hold immense promise as potent anticancer targets for GC treatment. [ABSTRACT FROM AUTHOR]

Background: Human pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection. Methods: We searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I2 statistics and publication bias was assessed using Begg and Mazumdar’s test. Meta-regression and subgroup analyses were performed to explore study heterogeneity. Results: In total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60–0.76), 0.73 (95% CI: 0.62–0.82), 2.57 (95% CI: 1.82–3.62), and 0.43 (95% CI: 0.34–0.54), 0.76 (95% CI: 0.72–0.80) and 6.01 (95% CI: 3.69–9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55–0.80), 0.88 (95% CI: 0.77–0.94), 5.80 (95% CI: 3.06–10.99), and 0.35 (95% CI: 0.24–0.51), 0.85 (95% CI: 0.82–0.88) and 16.50 (95% CI: 8.18–33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66–0.75), specificity of 0.79 (95% CI: 0.79–0.80), DOR of 6.92 (95% CI: 4.36–11.00), and AUC of 0.78 (95% CI: 0.72–0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51–0.60), specificity of 0.79 (95% CI: 0.76–0.82), DOR of 6.88 (95% CI: 2.30–20.60), and AUC of 0.77 (95% CI: 0.73–0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52–0.83), specificity of 0.84 (95% CI: 0.68–0.93), DOR of 11.51 (95% CI: 6.14–21.56), and AUC of 0.83 (95% CI: 0.80–0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72–0.85), specificity of 0.89 (95% CI: 0.85–0.93), DOR of 24.64 (95% CI: 6.95–87.37), and AUC of 0.87 (95% CI: 0.81–0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38–0.54), specificity of 0.93 (95% CI: 0.91–0.95), DOR of 19.86 (95% CI: 0.86–456.91), and AUC of 0.86 (95% CI: 0.52–1.00). Conclusion: SPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential publication bias and high heterogeneity of the included studies, further high quality studies are required in the future. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the most common malignant tumor types in the world and the majority of patients have already reached the advanced stage at the time of initial diagnosis, owing to the subtle symptoms of gastric cancer in the early stage and the low rate of screening in the population. Surgical resection is one of the main treatments for advanced gastric cancer; however, the efficacy of surgery is limited by factors such as low radical resection rate and high distant metastasis rate. A large number of clinical trials have indicated that neoadjuvant therapy (NAT), which consists of neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy and NAT combined with targeted therapy, may improve the therapeutic effect and prognosis of patients to different degrees. However, the benefit of NAT remains controversial due to the heterogeneity of clinical trials and gastric cancer itself. The present review summarizes the main research progress and key breakthrough of NAT for advanced gastric cancer and discusses its prospects. [ABSTRACT FROM AUTHOR]

Objective To evaluate the prognostic effects of neoadjuvant chemotherapy (NAC) in patients with local advanced gastric cancer. Methods We retrospectively analyzed prognosis in 191 patients with advanced gastric cancer, of whom 71 were treated with NAC and 120 received surgery only between February 2007 and July 2013. Postoperative complication rate was recorded. Survival by clinicopathological features, pathological T and N stages, and histopathological tumor regression was retrospectively compared between the two groups. Results According to Response Evaluation Criteria in Solid Tumors, none of the 71 patients in the NAC followed by surgery group showed complete response, 36 showed partial response, 25 had stable disease, and 10 had progressive disease. The chemotherapy response rate was 50.7%; the disease control rate was 85.9%. Grade 3/4 adverse events were seen in less than 20% patients, with acceptable toxicities. No difference was found in the overall postoperative complication rates between the two groups (7 versus 22 cases, P =0.18). Median survival time was significantly different, at 54 months in the NAC combined with surgery group and 25 months in the surgery-only group (P=0.025). Conclusion In patients with operable gastric adenocarcinomas, NAC can significantly improve overall survival without increasing surgical complications. [ABSTRACT FROM AUTHOR]

Eukaryotic translation initiation factor 5A2 (EIF5A2) plays an important role in tumor progression and prognosis evaluation. However, little information is available about its potential role in gastric cancer. This study aimed to investigate the function of EIF5A2 in tumor progression and its potential mechanisms. EIF5A2 expression was measured in human gastric cancer cell lines, the immortalized gastric mucosal epithelial cell line (GES-1) and human gastric cancer tissues and knocked down by RNA interference or upregulated by EIF5A2 plasmid transfection. Cell proliferation, migration and invasion were assessed in vitro. The downstream targets of EIF5A2 were examined by western blotting. EIF5A2 and its potential target metastasis-associated protein 1 (MTA1) expression were examined in 160 pairs of human gastric cancer and adjacent non-tumor specimens using immunohistochemistry (IHC) staining, and its correlation with clinicopathological features and survival was investigated. Knockdown of EIF5A2 or MTA1 caused an apparent suppression of HGC27 cell proliferation, migration and invasion. After knockdown of EIF5A2 in HGC27 cells, E-cadherin levels were upregulated and vimentin, cyclin D1, cyclin D3, C-MYC and MTA1 levels were downregulated. Upregulation of EIF5A2 in MKN45 cells resulted in the converse. IHC results showed a positive correlation between EIF5A2 and MTA1 expression in gastric cancers (P<0.001). Both EIF5A2 and MTA1 overexpression were correlated with pT stage (P=0.018 and P=0.042), pN stage (P=0.037 and P=0.020) and lymphovascular invasion (P=0.016 and P=0.044). EIF5A2 or MTA1 overexpression was significantly associated with poor overall survival and disease-free survival (All P<0.05). Multivariate analyses identified EIF5A2 as an independent predictor for both overall survival (P=0.012) and disease-free survival (P=0.008) in gastric cancer patients. Our findings indicate that EIF5A2 upregulation plays an important oncogenic role in gastric cancer. EIF5A2 may represent a new predictor for poor survival and is a potential therapeutic target for gastric cancer. [ABSTRACT FROM AUTHOR]

Background and Aims: The onco-protein c-fos was previously linked to favorable prognosis of gastric cancer (GC) without further validations. The present study was designed to address the issue based on a cohort of Chinese patients. Methods: Expression of c-fos was determined by immunohistochemical staining in specimens from 58 patients with GC who underwent surgical resection. The relationships between c-fos expression and clinicopathological and prognostic variables were further evaluated. Results: Expression of c-fos in tumor epithelia was observed in 39 (67.2%) patients. The protein was also positively expressed in lymphocytes within tumors and para-tumor epithelia. Tumors with positive expression of c-fos in tumor epithelia had a smaller size and marginally earlier T stage in all patients and/or those who underwent curative resection. Univariate analysis showed that patients with positive c-fos expression in tumor epithelia had significantly prolonged overall and tumor-free survival. Cox regression analysis revealed that c-fos expression in tumor epithelia was an independent or potential independent indicator of improved prognosis in different subgroups of patients. Expression of c-fos in para-tumor epithelia and intra-tumor lymphocytes was not associated with clinicopathological variables and long-term outcomes in patients. Conclusions: Our data demonstrated that c-fos expression was negatively associated with tumor progression and was predictive for favorable survival in patients with GC. [Copyright &y& Elsevier]