ABSTRACT
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 [HRâ=â1.72, 95% confidence interval (95% CI)â=â1.30-2.27], OS (HRâ=â1.87, 95% CIâ=â1.41-2.48), and cancer-specific survival (HRâ=â2.09, 95% CIâ=â1.04-4.21). The correlation was stronger in triple-negative breast cancer (TNBC) (OS: HRâ=â2.58, 95% CIâ=â1.63-4.06; DFS: HRâ=â3.51, 95% CIâ=â1.97-6.24). 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.
Subject(s)
Breast Neoplasms/blood , Breast Neoplasms/mortality , Lymphocyte Count/methods , Disease-Free Survival , Humans , Lymphocytes , Neutrophils , Prognosis , Triple Negative Breast Neoplasms/blood , Triple Negative Breast Neoplasms/mortalityABSTRACT
Metastasis is the major cause of death among gastric cancer (GC) patients, and altered expression of Ras-related protein RAP1B is associated with cancer development. The present study assessed RAP1B expression ex vivo and the effect of hypoxiainduced RAP1B overexpression on the promotion of the metastatic potential of GC cells in vitro. Immunohistochemistry was used to detect the expression of RAP1B and hypoxiainducible factor-1α (HIF-1α) in 178 GC tissue specimens. GC cell lines were used to assess the effects of hypoxia and RAP1B knockdown with RAP1B small interfering RNA (siRNA). Tumor cell viability was detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, invasion capacity was evaluated by a Transwell assay, and gene expression was determined by qRT-PCR and western blotting. The data showed that expression levels of RAP1B and HIF-1α proteins were high in the GC tissue specimens, and RAP1B expression was significantly associated with tumor-node-metastasis (TNM) stage and tumor size, while HIF-1α expression was significantly associated with TNM stage, Borrmann type and tumor differentiation. Moreover, RAP1B expression was associated with HIF-1α expression (r=0.547, P<0.001). The expression of RAP1B and HIF-1α proteins was associated with a shorter overall survival of patients according to the univariate analysis (log-rank test, P<0.01), and RAP1B expression and TNM stage were independent prognostic predictors in patients using a multivariate analysis (P<0.001). In vitro, hypoxia induced the invasion of GC cells and the expression of RAP1B and HIF-1α (P<0.05); whereas knockdown of RAP1B expression using siRNA inhibited the tumor cell invasion capacity even under hypoxic culture conditions (P<0.05). In conclusion, the protein expression of RAP1B and HIF-1α contributed to GC malignant behavior and poor prognosis. Future studies will evaluate whether targeting RAP1B expression can be used as a novel strategy to control GC or as a biomarker for prognosis prediction.
