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BackgroundAs a kind of small membrane vesicles, exosomes are secreted by most cell types from multivesicular endosomes, including tumor cells. The relationship between exosomes and immune response plays a vital role in the occurrence and development of tumors. Nevertheless, the interaction between exosomes and the microenvironment of tumors remains unclear. Therefore, we set out to study the influence of exosomes on the triple-negative breast cancer (TNBC) microenvironment.MethodOne hundred twenty-one exosome-related genes were downloaded from ExoBCD database, and IVL, CXCL13, and AP2S1 were final selected because of the association with TNBC prognosis. Based on the sum of the expression levels of these three genes, provided by The Cancer Genome Atlas (TCGA), and the regression coefficients, an exosome risk score model was established. With the median risk score value, the patients in the two databases were divided into high- and low-risk groups. R clusterProfiler package was employed to compare the different enrichment ways between the two groups. The ESTIMATE and CIBERSORT methods were employed to analyze ESTIMATE Score and immune cell infiltration. Finally, the correlation between the immune checkpoint-related gene expression levels and exosome-related risk was analyzed. The relationship between selected gene expression and drug sensitivity was also detected.ResultsDifferent risk groups exhibited distinct result of TNBC prognosis, with a higher survival rate in the low-risk group than in the high-risk group. The two groups were enriched by immune response and biological process pathways. A better overall survival (OS) was demonstrated in patients with high scores of immune and ESTIMATE rather than ones with low scores. Subsequently, we found that CD4+-activated memory T cells and M1 macrophages were both upregulated in the low-risk group, whereas M2 macrophages and activated mast cell were downregulated in the low-risk group in patients from the TCGA and GEO databases, respectively. Eventually, four genes previously proposed to be targets of immune checkpoint inhibitors were evaluated, resulting in the expression levels of CD274, CTLA4, LAG3, and TIM3 being higher in the low-risk group than high-risk group.ConclusionThe results of our study suggest that exosome-related risk model was related to the prognosis and ratio of immune cell infiltration in patients with TNBC. This discovery may make contributions to improve immunotherapy for TNBC.

ObjectivesSome studies have identified tumour-infiltrating lymphocytes (TILs) in H&E-stained sections of gastric cancer, but the prognostic and clinicopathological significance of this remains unclear. The objective of this study is to evaluate the associations between H&E-based TIL density and prognosis and clinicopathological characteristics of patients with gastric cancer.DesignSystematic review and meta-analysis.Data sourcesCochrane Library, PubMed and Embase databases were searched through 25 February 2020.Eligibility criteriaStudies evaluating the correlations between TILs assessed by H&E-stained sections and prognosis and clinicopathological characteristics of gastric cancer were included.Data extraction and synthesisRelevant data were extracted and risks of bias were assessed independently by two reviewers. HR and relative risk (RR) with 95% CI were pooled by random-effect models to estimate the associations between TIL density and overall survival (OS) and clinicopathological characteristics, respectively.ResultsWe enrolled nine studies including 2835 cases for the present meta-analysis. High TILs were associated with superior OS (HR=0.68, 95% CI 0.52 to 0.87, p=0.003) compared with low TILs. High TILs were significantly associated with lower depth of invasion (T3–T4 vs T1–T2) (RR=0.58, 95% CI 0.50 to 0.66, pConclusionsOur meta-analysis suggests that H&E-based TIL density is a reliable biomarker to predict the clinical outcomes of patients with gastric cancer. Multicentre, prospective studies are needed to further confirm our findings.PROSPERO registration numberCRD42020169877.

Metabolic reprogramming has become a hot topic recently in the regulation of tumour biology. Although hundreds of altered metabolic genes have been reported to be associated with tumour development and progression, the important prognostic role of these metabolic genes remains unknown. We downloaded messenger RNA expression profiles and clinicopathological data from The Cancer Genome Atlas and the Gene Expression Omnibus database to uncover the prognostic role of these metabolic genes. Univariate Cox regression analysis and lasso Cox regression model were utilized in this study to screen prognostic associated metabolic genes. Patients with high-risk demonstrated significantly poorer survival outcomes than patients with low-risk in the TCGA database. Also, patients with high-risk still showed significantly poorer survival outcomes than patients with low-risk in the GEO database. What is more, gene set enrichment analyses were performed in this study to uncover significantly enriched GO terms and pathways in order to help identify potential underlying mechanisms. Our study identified some survival-related metabolic genes for rectal cancer prognosis prediction. These genes might play essential roles in the regulation of metabolic microenvironment and in providing significant potential biomarkers in metabolic treatment.

// Jun Wang 1,* , Jianpeng Chen 2,* , Yan Guo 3 , Baocheng Wang 1 and Huili Chu 1 1 Department of Oncology, General Hospital, Jinan Command of the People’s Liberation Army, Jinan, China 2 Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China 3 Department of Outpatient, Military Command of Shandong Province, Jinan, China * These authors have contributed equally to this work Correspondence to: Jun Wang, email: // Keywords : NSCLC, angiogenesis, antiangiogenic agents, bevacizumab Received : January 06, 2017 Accepted : April 27, 2017 Published : May 17, 2017 Abstract Tumor angiogenesis is a frequent event in the development and progression of non-small cell lung cancer (NSCLC) and has been identified as a promising therapeutic target. The vascular endothelial growth factor (VEGF) family and other angiogenic factors, including fibroblast growth factor and platelet-derived growth factor, promote the growth of newly formed vessels from preexisting vessels and change the tumor microenvironment. To date, two antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab, which target VEGF-A and its receptor VEGF receptor-2, respectively, have been approved for the treatment of locally advanced or metastatic NSCLC when added to first-line standard chemotherapy. Numerous oral multitargeting angiogenic small molecule tyrosine kinase inhibitors (TKIs) have been widely evaluated in advanced NSCLC, but only nintedanib in combination with platinum-based doublet chemotherapy has demonstrated a survival benefit in the second-line setting. Additionally, small-molecule TKIs remain the standard of care for patients with mutated EGFR, ALK or ROS1. Moreover, immune checkpoint inhibitors that target the programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) are changing the current strategy in the treatment of advanced NSCLC without driver gene mutations. The potential synergistic activity of antiangiogenic agents and TKIs or immunotherapy is an interesting topic of research. This review will summarize the novel antiangiogenic agents, antiangiogenic monotherapy, as well as potential combination therapeutic strategies for the clinical management of advanced NSCLC.

Our study observed the relationship between transient receptor potential melastatin 7 (TRPM7) expression and the metastatic process of nasopharyngeal carcinoma (NPC). We found that TRPM7 was overexpressed in 102 out of 206 (49.5%) human NPC cases and was significantly associated with clinical stage and lymphatic and distant metastasis. The results suggested that TRPM7 promotes NPC cell migration and invasion in vitro. Further, TRPM7 was correlated with poor clinical outcome and was an independent predictor for 5-year overall survival rate (HR, 1.832; 95% CI, 1.237–4.146 [P = 0.041]). In conclusion, TRPM7 promotes the metastasis of NPC and may serve as a prognostic marker in NPC patients.

Standard cytotoxic chemotherapy has limited efficacy in advanced insulinomas, and control of blood glucose concentrations in these patients may be difficult. This article describes an elderly (74-year-old) man with metastatic insulinoma and severe hypoglycemia who was treated with repeated 6-week cycles of oral sunitinib malate (25 mg/day for 4 weeks, followed by 2 weeks off treatment). After treatment for more than 2 years, his condition improved and he continued to have a good quality of life with no evidence of tumor progression based on PET/CT findings. Although sunitinib treatment lowered the patient's blood glucose concentrations further and induced repeated symptomatic hypoglycemic episodes, he was able to tolerate the treatment well after changing the timing of sunitinib dosing and adjusting his diet.

BACKGROUND AND OBJECTIVE: Blood vessel invasion plays a very important role in the progression and metastasis of cancer. However, blood vessel invasion as a prognostic factor for survival in non-small cell lung cancer (NSCLC) remains controversial. The aim of this study is to explore the relationship between blood vessel invasion and outcome in patients with NSCLC using meta-analysis. METHODS: A meta-analysis of published studies was conducted to investigate the effects of blood vessel invasion on both relapse-free survival (RFS) and overall survival (OS) for patients with NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the strength of this association. RESULTS: A total of 16,535 patients from 52 eligible studies were included in the systematic review and meta-analysis. In total, blood vessel invasion was detected in 29.8% (median; range from 6.2% to 77.0%) of patients with NSCLC. The univariate and multivariate estimates for RFS were 3.28 (95% CI: 2.14-5.05; P

The aim of this study was to investigate prognostic significance of TRPM7 expression in nasopharyngeal carcinoma (NPC) and evaluate the association of TRPM7 with tumor invasion and metastasis. Immunohistochemical staining for TRPM7 was carried out on paraffin-embedded tissue sections from 206 NPC patients. The data was subjected to statistical analysis with respect to clinicopathological variables and survival. Real-time PCR and Western blot were used to assess the expression of TRPM7 in NPC cells. Small interfering RNA and construct transfection were used to knockdown and improve TRPM7 expression in NPC cells. TRPM7 was highly expressed in 102 out of 206 (49.5%) NPC cases. TRPM7 expression was significantly correlated with clinical stage, lymphatic and distant metastasis. The patients who had high TRPM7 expression showed a significantly lower 5 year survival rate than the patients who had low TRPM7 expression. TRPM7 might be an independent prognostic indicator for patient's survival. The cell lines with high metastatic potential expressed more TRPM7 than the cell lines with low metastatic potential. Moreover, the migratory and invasive potential of NPC cells was significantly decreased and increased by TRPM7 knockdown and overexpression. The study indicates that TRPM7 expression is inversely correlated with NPC patient survival and correlated with NPC invasion and metastasis. Note: This abstract was not presented at the meeting. Citation Format: Jian-Peng Chen, Guiqin Sun, Wei-Bo Wang, Cai-Xia Wang. TRPM7 expression predicts poor prognosis in patients with nasopharyngeal carcinoma and correlates with tumor metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 42. doi:10.1158/1538-7445.AM2014-42