Jingkun Qu

Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway

Invasion and metastasis are the major causes of tumor-related mortality in lung cancer. It is believed that curcumin is an effective drug possessing anti-invasive and anti-metastatic activities in the treatment of cancer. However, the specific mechanisms remain unclear. In the present study, we investigated whether the PKCα/Nox-2/ATF-2/MMP-9 signaling pathway is involved in the invasive behavior of lung cancer and whether curcumin could inhibit invasion by modulating this pathway. The cytotoxic effect of curcumin was evaluated by MTT assay and the capacity of invasion was assessed by Transwell assay. siRNA and plasmid transfection techniques were used to study the function of targeted genes. Real-time PCR and western blot analysis were used to evaluate the expression levels of PKCα, Nox-2, MMP-9 and the phosphorylation of ATF-2. The results showed that curcumin inhibited the proliferation and invasion of A549 cells in a dose-dependent manner. Overexpression of MMP-9 enhanced the invasion of A549 cells. However, inhibition of MMP-9 by siRNA or curcumin suppressed cell invasion. Moreover, we also demonstrated the catalytic role of PKCα in expression of MMP-9 and cellular invasion in A549 cells, which was dependent on the expression of Nox-2 and phosphorylation of ATF-2. Finally, we also showed that curcumin dose-dependently reduced the expression of PKCα, P47phox, Nox-2 and phosphorylated ATF-2, as well as intracellular ROS generation, suggesting the inhibitory effect of curcumin on the activation of the PKCα/Nox-2/ROS/ATF-2 pathway. In conclusion, the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway is activated in lung cancer A549 cells, which could be modulated by curcumin to inhibit cell invasiveness.

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.

Clinicopathological and prognostic significance of c-Met overexpression in breast cancer

BACKGROUND c-Met has been shown to promote organ development and cancer progression in many cancers. However, clinicopathological and prognostic value of c-Met in breast cancer remains elusive. METHODS PubMed and EMBASE databases were searched for eligible studies. Correlation of c-Met overexpression with survival data and clinicopathological features was analyzed by using hazard ratio (HR) or odds ratio (OR) and fixed-effect or random-effect model according to heterogeneity. All statistical tests were two-sided. RESULTS 32 studies with 8281 patients were analyzed in total. The c-Met overexpression was related to poor OS (overall survival) (HR=1.65 (1.328, 2.051)) of 18 studies with 4751 patients and poor RFS/DFS (relapse/disease free survival) (HR=1.53 (1.20, 1.95)) of 12 studies with 3598 patients. Subgroup analysis according to data source/methods/ethnicity showed c-Met overexpression was related to worse OS and RFS/DFS in Given by author group, all methods group and non-Asian group respectively. Besides, c-Met overexpression was associated with large tumor size, high histologic grade and metastasis. CONCLUSIONS Our results showed that c-Met overexpression was connected with poor survival rates and malignant activities of cancer, including proliferation, migration and invasion, which highlighted the potential of c-Met as significant candidate biomarker to identify patients with breast cancer at high risk of tumor death.Background c-Met has been shown to promote organ development and cancer progression in many cancers. However, clinicopathological and prognostic value of c-Met in breast cancer remains elusive. Methods PubMed and EMBASE databases were searched for eligible studies. Correlation of c-Met overexpression with survival data and clinicopathological features was analyzed by using hazard ratio (HR) or odds ratio (OR) and fixed-effect or random-effect model according to heterogeneity. All statistical tests were two-sided. Results 32 studies with 8281 patients were analyzed in total. The c-Met overexpression was related to poor OS (overall survival) (HR=1.65 (1.328, 2.051)) of 18 studies with 4751 patients and poor RFS/DFS (relapse/disease free survival) (HR=1.53 (1.20, 1.95)) of 12 studies with 3598 patients. Subgroup analysis according to data source/methods/ethnicity showed c-Met overexpression was related to worse OS and RFS/DFS in Given by author group, all methods group and non-Asian group respectively. Besides, c-Met overexpression was associated with large tumor size, high histologic grade and metastasis. Conclusions Our results showed that c-Met overexpression was connected with poor survival rates and malignant activities of cancer, including proliferation, migration and invasion, which highlighted the potential of c-Met as significant candidate biomarker to identify patients with breast cancer at high risk of tumor death.

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.