Jizhao Wang

Prognostic significance of tumor-associated macrophages in breast cancer: a meta-analysis of the literature

Purpose Tumor associated macrophages (TAMs) are important prognostic factors and have been proved to be associated with the invasion and migration of various cancer. However, the relationship between TAMs and breast cancer outcomes remains unclear. Experimental Design Sixteen studies with a total of 4,541 breast cancer patients were included in this meta-analysis. Correlation of TAMs with overall survival (OS), disease-free survival(DFS), relapse-free survival (RFS), breast cancer special survival (BCSS) and clinicopathological features were analyzed. Survival data and clinicopathological value were integrated by analyzing hazard ratio(HR) and odds ratio(OR) separately and using Fixed-effect or Random-effect model according to heterogeneity. All statistical tests were two-sided. Results OS and DFS were correlated with high density of TAMs with HR= 1.504(1.200, 1.884)/ 2.228(1.716, 2.892) respectively. And subgroup analysis of location and biomarker in OS and DFS group showed prognosis was associated with TAMs distribution and biomarker selection. Besides, TAMs high infiltration was significantly related to age, size, histologic grade, ER/PR status, basal phenotype and vascular invasion. Conclusion High density of TAMs was associated with poor survival rates of breast cancer. TAMs in stroma are associated with worse outcome than that in nest and using CD68 as a biomarker for TAMs to evaluate the risk is better than CD163 or CD206 alone. Moreover, high infiltration of TAMs was significantly associated with negative hormone receptor status and malignant phenotype. TAMs infiltration can serve as a novel prognostic factor in breast cancer patients.

High Infiltration of Tumor-Associated Macrophages Influences Poor Prognosis in Human Gastric Cancer Patients, Associates With the Phenomenon of EMT.

AbstractTumor-associated macrophages (TAMs) are associated with poor prognosis in numerous human cancers and play important roles in tumor progression. Epithelial-mesenchymal transition (EMT) contributes to invasion and metastasis in cancer. However, the associations between TAMs and EMT are not clear in gastric cancer (GC). The present study was designed to investigate the effects of TAMs on EMT in human GC.TAMs marker CD68 and EMT-related proteins were detected by immunohistochemistry (IHC) in human GC tissues and their clinical significance were evaluated.A high level of infiltration of TAMs was associated with aggressive characteristics of tumor and an independent poor prognostic factor in human GC tissues. Infiltration of TAMs was also associated with EMT-related proteins in human GC tissues.Our findings suggest that the high level of infiltration TAMs was associated with aggressive features of GC and is an independent poor prognostic factor in GC patients. TAMs are associated with EMT induction in human GC tissues. The level of TAMs infiltration may be used as a prognostic factor and even a therapeutic target in GC.

High tumor-associated macrophages infiltration is associated with poor prognosis and may contribute to the phenomenon of epithelial–mesenchymal transition in gastric cancer

Background Recent studies show that epithelial–mesenchymal transition (EMT) and tumor-associated macrophages (TAMs) contribute to the progression and poor prognosis of carcinoma through multiple mechanisms. Both inflammation and changing of epithelium have a close relationship with tumorigenesis of gastric cancer. However, the relevance between EMT and TAMs is still unclear in gastric cancer and needs more scientific research. This study is designed to explore the relationship between EMT and TAMs in gastric cancer. Materials and methods Immunohistochemistry was used to detect the expression of EMT-related proteins and TAM markers in cancer tissues and normal gastric tissues. Results High levels of EMT and TAMs infiltration are related to aggressive features and independent prognostic factors in gastric cancer, respectively. In addition, expression of the two indicators is associated with expression of transforming growth factor-β1 (TGF-β1). Infiltration of TAMs is also associated with EMT-related marker in gastric cancer. Conclusion Our results suggest that high levels of EMT and TAMs infiltration are related to aggressive features and independent prognostic factors in gastric cancer, respectively. A correlation was found between EMT- and TAM-related indicators, which may be associated with TGF-β signaling pathway. The level of TAMs infiltration plays an important role in gastric cancer, the markers of which can be used as prognostic indicators.

Low expression of Rap1GAP is associated with epithelial-mesenchymal transition (EMT) and poor prognosis in gastric cancer

Rap1GAP is a crucial tumor suppressor, but its role in gastric cancer (GC) is little investigated. In this study, we found that the expression of Rap1GAP was decreased in GC. Low expression of Rap1GAP was positively correlated with advanced pTNM stage, Borrmann types, tumor diameter and poor prognosis in patients with GC. Low expression of Rap1GAP correlated with loss of E-cadherin expression, and anomalous positivity of MMP2 expression. Multivariate analysis showed that low expression of Rap1GAP was an independent prognostic factor. Ectopic expression of Rap1GAP impaired cell migration and invasion, promoted the expression of E-cadherin and decreased the expression of MMP2. These results suggest that Rap1GAP functions as a novel suppressor of EMT and tumor metastasis in GC, and loss of Rap1GAP predicts poor prognosis in GC.

Prognostic role of pretreatment neutrophil to lymphocyte ratio in breast cancer patients: A meta-analysis

Background: Inflammation and cancer are closely related to each other. As a parameter that can reflect inflammation and host immune reaction, elevated blood neutrophil to lymphocyte ratio (NLR) has been confirmed to be correlated with poor prognosis in a variety of cancers. However, this remains controversial in breast cancer. Thus, we performed this updated meta-analysis to further clarify whether high NLR could be a predictor of survival in breast cancer patients. Methods: We searched on PubMed Database and Cochrane Library. Overall survival (OS), disease-free survival (DFS), and cancer-specific survival were used as outcome events, and hazard ratio (HR) was chosen as the parameter to evaluate the correlation. Result: Eighteen eligible studies were involved in this meta-analysis. The synthesized analysis demonstrated that elevated NLR was associated with poor DFS [HR = 1.72, 95% confidence interval (95% CI) = 1.30–2.27], OS (HR = 1.87, 95% CI = 1.41–2.48), and cancer-specific survival (HR = 2.09, 95% CI = 1.04–4.21). The correlation was stronger in triple-negative breast cancer (TNBC) (OS: HR = 2.58, 95% CI = 1.63–4.06; DFS: HR = 3.51, 95% CI = 1.97–6.24). Conclusion: Higher NLR was correlated to poor prognosis of breast cancer patients. As a clinical parameter that we can easily obtain, NLR might be a potential predictor in patients’ survival to assist with physicians’ treatment decisions.

Roles of LPA receptor signaling in breast cancer

ABSTRACT Introduction: LPA and its receptors play an important role in mediating malignant behaviors in various cancers, including breast cancer. Aberrant expression of certain LPA receptors in breast cancer suggested that LPA receptors could be potential biomarkers in understanding malignant growth patterns of breast cancer. Further research considering molecular mechanisms for LPA receptors will contribute to new methods of malignant breast cancer diagnosis and treatment. Areas covered: Accumulating studies have indicated that LPA receptors correlated to proliferation, invasion, migration and metastasis both in vivo and in vitro. In this manuscript, we have reviewed LPA receptors expressions and LPA mediated biological behaviors in cell lines, mouse models and patients and their potential molecular pathways. Expert commentary: LPA receptors could be applied in early diagnosis, survival rate prediction, metastasis probability and potential treatment targets. However, further studies are required to clarify the upstream and downstream molecular mechanisms of LPA receptors in breast cancer.

MYC overexpression with its prognostic and clinicopathological significance in breast cancer

Background Proto-oncogene MYC has been indicated to promote progression of many cancers. However, prognostic and clinicopathological significance of MYC in breast cancer need further evaluation. Methods We searched EMBASE and PubMed databases to find useful studies. We analyzed relationships between high MYC expression and prognostic data/ clinicopathological features through hazard ratio (HR) and odds ratio (OR). Each statistical test was two-sided. Results There were 29 studies (36 cohorts) with 12621 patients enrolled in our study The MYC overexpression was associated with worse DFS/RFS (disease/relapse free survival) in 11 studies (16 cohorts) with 5390 patients, and OS (overall survival) of 7 studies (8 cohorts) with 2672 patients. Subgroup analysis according to ethnicity/technique/data source displayed that MYC overexpression was associated with poor DFS/RFS in FISH, other technique, all data source and Asian/Non-Asian subgroup, and worse OS in all subgroups. In addition, MYC overexpression was related to large tumor size, high histologic grade, lymph node metastasis, negative hormone receptors and positive Ki67 expression. Conclusions Our results showed that MYC overexpression was associated with worse prognosis and high risk of breast cancer, especially in patients with negative hormone receptors, which highlighted the potential of MYC as a significant prognostic biomarker of breast cancer.

Plasma phospholipase A2 activity may serve as a novel diagnostic biomarker for the diagnosis of breast cancer

Previous studies have indicated that phospholipase A2 (PLA2) may be associated with tumorigenesis in human tissues. The present study aimed to investigate the association between plasma PLA2 activity and the breast cancer (BC) status of patients. Increased plasma PLA2 activity was detected in patients with breast cancer when compared with healthy controls. Plasma samples were obtained from patients with BC (n=169), patients with benign disease (BD; n=80) and healthy controls (n=81). PLA2 activity was assessed using a quantitative fluorescent assay with selective inhibitors. It was demonstrated that increased PLA2 and secretory PLA2 (sPLA2) activity was associated with tumor stage, particularly in patients with late-stage disease. Additionally, smoking, alcohol consumption, body mass index (BMI) and age of patients did not have a significant effect on PLA2 activity. Analysis of receiver operating characteristic curves revealed that plasma PLA2 and sPLA2 activities were increased in BC patients compared with healthy controls. It was concluded that plasma PLA2 activity may serve as a biomarker for patients with BC.

Survival analysis for male ductal and lobular breast cancer patients with different stages

AIM We aimed to investigate risk factors and current treatment effects in male breast cancer patients. METHODS Kaplan-Meier plot, log-rank test, COX model, nomograms and propensity score matching were used. RESULTS Among stage I-III patients, surgery was associated with better prognosis. In subgroup analysis, performing surgery and no radiation or chemotherapy led to worse prognosis in research group. Among stage IV patients, chemotherapy correlated with better prognosis and radiation led to better breast cancer-specific survival. In addition, brain and liver metastasis correlated with worse prognosis; and lung correlated with worse breast cancer-specific survival. CONCLUSION For stage I-III patients, surgery and chemotherapy were recommended. And not applying radiation or chemotherapy could be carefully considered for ER(+) HER-2(-) patients. For stage IV patients, chemotherapy and radiation were commended.

Prognostic value of FOXQ1 in patients with malignant solid tumors: a meta-analysis

Background Forkhead box Q1 (FOXQ1, also known as HFH1), a member of the forkhead transcription factor family, has been demonstrated to be overexpressed in multiple tumors and is thought to be an indicator of poor clinical outcomes. Methods A meta-analysis using qualified relevant literature was performed to evaluate the prognostic significance of FOXQ1 in various malignant solid tumors. A search of electronic databases was conducted in MEDLINE, Embase, and the Cochrane Library to identify relevant studies published from 1966 to July 30, 2016, and the studies were identified by further evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for analyses were assessed to investigate the association between FOXQ1 expression and overall survival (OS) of patients with malignant solid tumors. Results A total of 1,520 patients from six studies (seven cohorts) with multiple malignant solid tumors were included. For OS, high FOXQ1 expression could significantly predict worse outcome with the pooled HR of 1.38 (95% CI: 1.17–1.59; P<0.001). The subgroup analysis suggested that the elevated levels of FOXQ1 appear to be associated with worse OS in hepatocellular carcinoma (HR =1.34; 95% CI: 1.11–1.57; P<0.001) and other cancers (HR =1.62; 95% CI: 1.09–2.14; P<0.001). Conclusion This meta-analysis indicated that the high expression of FOXQ1 is associated with an adverse OS in malignant solid tumors, suggesting that FOXQ1 may be a predictor of poor prognosis for the development of malignant solid tumors.