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Purpose: Immunotherapy for gastrointestinal stromal tumors (GISTs) remains a clinical challenge. The present study aimed to explore the clinical and prognostic significance of immune cell infiltration and PD-L1 expression in GISTs. Methods: A total of 507 clinical tissue specimens of primary GISTs were collected for immunohistochemical analysis of immune cell infiltration and PD-L1 expression. Influencing factors of survival were evaluated by Kaplan–Meier analysis. Univariate and multivariate analyses were performed using the Cox regression model. Results: There were significant differences in sex, tumor location, size, mitotic index, NIH risk grade, and cell morphology between different gene mutation types of GISTs. Immune cell infiltration in GISTs mainly involved macrophages and T cells. PD-1 was expressed in 48.5% of the tissue specimens, and PD-L1 expression was detected in 46.0% of the samples. PD-L1 expression was negatively correlated with the tumor size and mitotic index but positively correlated with the number of CD8+ T cells. There were significant differences in the number of CD8+ T cells between different gene mutation types. Wild type-mutant GISTs were enriched with CD8+ T cells as compared with KIT- and PDGFRA-mutant GISTs. The number of CD8+ T cells was higher in non-gastric GISTs. PD-L1 and CD8+ T cells were independent predictors for better relapse-free survival of GISTs. Conclusions: PD-L1 expression is a predictive biomarker for better prognosis of GISTs. Non-gastric GIST patients with wild-type mutations may be the beneficiaries of PD-1/PD-L1 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Limited data exist on VTE risk and prophylaxis in Chinese inpatients. The Identification of Chinese Hospitalized Patients' Risk Profile for Venous Thromboembolism-2 (DissolVE-2), a nationwide, multicenter, cross-sectional study, was therefore designed to investigate prevalence of VTE risks and evaluate VTE prophylaxis implementation compliant with the latest prophylaxis guidelines (American College of Chest Physicians [CHEST], 9th edition).Methods: Adults admitted (≥ 72 h) to 60 urban, tertiary Chinese hospitals due to acute medical conditions or surgery from March to September 2016 were assessed for VTE risk. Risk assessments were made by using the Padua Prediction Scoring or Caprini Risk Assessment model, risk factors, and prophylaxis based on the CHEST guidelines, 9th edition.Results: A total of 13,609 patients (6,986 surgical and 6,623 medical) were analyzed. VTE risk in surgical inpatients was categorized as low (13.9%; 95% CI, 13.1-14.7), moderate (32.7%; 95% CI, 31.6-33.8), and high (53.4%; 95% CI, 52.2-54.6); risk in medical patients was categorized as low (63.4%; 95% CI, 62.2-64.6) and high (36.6%; 95% CI, 35.4-37.8). Major risk factors in surgical and medical patients were major open surgery (52.6%) and acute infection (42.2%), respectively. Overall rate of any prophylaxis and appropriate prophylactic method was 14.3% (19.0% vs 9.3%) and 10.3% (11.8% vs 6.0%) in surgical and medical patients.Conclusions: A large proportion of hospitalized patients reported VTE risk and low rate of CHEST-recommended prophylaxis. The data highlight the insufficient management of VTE risk and show the great potential for improving physicians' awareness and current practices across China.Trial Registry: Chinese Clinical Trial Registry; No.: ChiCTR-OOC-16010187; URL: http://www.chictr.org.cn/showproj.aspx?proj=17077. [ABSTRACT FROM AUTHOR]

Abstract: Background: Tumor necrosis factor receptor‐associated factor 2 (TRAF2) is a key effector in the activation of nuclear factor kappa B (NF‐κB). Nevertheless, the role of TRAF2 in gastric tumorigenesis remains little defined. Methods: Immunohistochemistry was used to find the relationship between TRAF2 expression and clinicopathological characteristics of gastric cancer patients, and nomogram was applied to predict the overall survival of patients. Besides, we performed transwell assays to detect the function of TRAF2 in promoting metastasis and explored the correlations between TRAF2, NF‐κB, and interleukin‐8 (IL‐8) in vitro. In addition, we examined the correlation between TRAF2 and tumor microenvironment by immunohistochemistry staining. Results: In our study, we found that TRAF2 expression was markedly increased in gastric cancer tissues. High intratumoral TRAF2 staining, which was associated with tumor invasion and metastasis, was also an independent poor prognosticator for gastric cancer patients. In vitro studies revealed that TRAF2 enhanced NF‐κB activation and subsequent IL‐8 expression in gastric cancer cells. Inhibition of NF‐κB or IL‐8 signaling attenuated TRAF2‐induced migration and invasion abilities. High TRAF2 expression was confirmed to be associated with both high intratumoral and serum levels of IL‐8. In addition, TRAF2 expression was positively correlated with neutrophil and macrophage infiltration as well as microvessels formation in gastric cancer samples. Conclusions: These results suggest that TRAF2 functions as an important modulator in tumor metastasis and tumor microenvironment formation and is a novel independent prognostic factor of gastric cancer. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated the clinical significance of polarized tumor-associated macrophages (TAMs) in gastric cancer whereas the cytokines orchestrating TAM polarization remain elusive. This study aims to evaluate the prognostic value of C-C motif ligand 2 (CCL2) expression in gastric cancer patients after surgery. We examined CCL2 expression in tumor tissues by immunohistochemical staining in retrospectively enrolled 414 gastric cancer patients receiving gastrectomy at Zhongshan Hospital during 2008. We used Kaplan-Meier analysis and Cox regression models to assess the prognostic value of CCL2 expression. We generated a predictive nomogram from integrating CCL2 expression with the TNM staging system to evaluate 3- and 5-year overall survival. High intratumor CCL2 expression associated with adverse clinical outcome. Intratumor CCL2 expression provided additional prognostic value in gastric cancer patients. CCL2 expression, as well as well-established TNM staging parameters, was identified as independent prognostic factor for overall survival. The generated nomogram corresponded well with the ideal model in predicting the 3- and 5-year overall survival of gastric cancer patients. CCL2, an identified potential independent adverse prognosticator, could be integrated with TNM staging system to improve the predictive accuracy for overall survival in gastric cancer patients especially with advanced stages. [ABSTRACT FROM AUTHOR]

Background: CXC chemokine receptor 2 (CXCR2) has been reported to play an important role in the proliferation and invasion of gastric cancer cells. The present study aims to investigate the impact of CXCR2 expression on the overall survival (OS) of gastric cancer patients after radical resection.Methods: Intratumoral CXCR2 expression was evaluated with immunohistochemistry on tissue microarrays containing tumor samples of 357 gastric cancer patients from a single center. CXCR2 expression levels were correlated to clinicopathological variables and OS.Results: CXCR2 expression was mainly located in the cytoplasm of gastric carcinoma cells. High CXCR2 expression was associated with poor tumor differentiation (p = 0.021), increased tumor depth (p < 0.001), lymph node metastasis (p < 0.001), advanced TNM stage (p < 0.001) and short OS (p = 0.001). CXCR2 expression was an independent prognostic factor for OS (p = 0.001) in multivariate analysis, and could be combined with TNM stage to generate a predictive nomogram for clinical outcome in patients with gastric cancer.Conclusion: Intratumoral CXCR2 expression is a novel independent predictor for survival in gastric cancer patients. CXCR2 might be a promising therapeutic target of postoperative adjuvant treatment. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The aims of this study were to evaluate the relationship between SLC22A18 expression and clinicopathologic features while investigate the prognostic value of SLC22A18 expression in breast cancer after surgery. Specimens and methods: Immunohistochemistry was used to examine SLC22A18 protein expression in the breast tumors. Prognostic value of SLC22A18 protein and other clinicopathologic factors were evaluated. The Kaplan–Meier method and the Cox proportional hazards model were used to predict factors with a significant independent prognostic value. Digital image analysis was employed to quantify immunostaining. Results: SLC22A18 expression was correlated with tumor size, lymph node metastasis, clinical stage, and extensive lyphovascular invasion. The results of Kaplan–Meier analysis indicated that SLC22A18 expression was associated with relapse-free survival (RFS) of breast cancer. The survival of higher expression SLC22A18 group had longer cum survival compared to the group with low expression. The difference was significant (p =0.003, log-rank test). Cox''s regression analysis showed that tumor size, lymph nodes metastasis, nuclear stage, extensive lymphovascular invasion, and SLC22A18 expression might be used as prognostic factor for RFS. Nuclear stage and SLC22A18 expression were the most meaningful histopathologic parameter in predicting tumor recurrence. Compared with the group of higher SLC22A18 expression, the lower expression group was more likely to relapse. The HR is 2.624 (p =0.035). Conclusion: Low expression of SLC22A18 was associated with tumor progression, recurrence and poor survival after breast surgery. Testing expression of SLC22A18 will be helpful for predicting prognosis in breast cancer. [Copyright &y& Elsevier]