Lactate dehydrogenase A (LDHA) is involved in a variety of cancers. The purpose of this study was to investigate the expression, prognostic roles and function of LDHA in breast cancer. We found that LDHA was upregulated in both breast cancer cell lines and clinical specimens using quantitative real-time PCR (qRT-PCR). Immunohistochemistry (IHC) analysis of tissue microarrays (TMAs) showed that high LDHA expression was associated with cell proliferation, metastasis and poor patient overall survival (OS) and disease free survival (DFS). Furthermore, we found that LDHA promoted glycolysis and cell proliferation in vitro and in vivo. We also performed luciferase reporter assays and found that LDHA was a direct target of miR-34a. Repression of LDHA by miR-34a suppressed glycolysis and cell proliferation in breast cancer cells in vitro. Our findings provide clues regarding the role of miR-34a as a tumor suppressor in breast cancer through the inhibition of LDHA both in vitro and in vivo. Targeting LDHA through miR-34a could be a potential therapeutic strategy in breast cancer.
Elevated preoperative plasma fibrinogen was independently associated with poor prognosis in breast cancer patients and may serve as a valuable parameter for risk assessment in breast cancer patients.
BackgroundTo evaluate the prognostic effect of log odds of positive lymph nodes (LODDS) and develop a nomogram for survival prediction in breast cancer patients at the time of surgery.ResultsLODDS was an independent risk factor for cancer-related death in breast cancer (hazard ratio: 1.582, 95%CI: 1.190-2.104). Menopausal status, tumor size, pathological lymph node staging, estrogen receptor status and human epidermal growth factor receptor-2 status were also included in the nomogram. The calibration plots indicated optimal agreement between the nomogram prediction and actual observation. Discrimination of nomogram was superior to the seventh edition TNM staging system [C-index: 0.745 vs. 0.721 (p = 0.03) in training cohort; 0.796 vs. 0.726 (p < 0.01) in validation cohort].MethodsWe retrospectively evaluated 2023 breast cancer patients from Jan 2002 to Dec 2008 at our center. The cohort was randomly divided into training cohort and validation cohort. Univariate and multivariate analyses were performed to identify prognostic factors, and nomogram was established using Cox regression model in training cohort. External validation of the nomogram was performed in the validation cohort.ConclusionsThe LODDS is an independent prognostic indicator in breast cancer and the novel nomogram can provide individual prediction of cancer-specific survival and help prognostic assessment for breast cancer patients.
Growing evidence showed that inflammation response plays an important role in cancer development and progression, and absolute lymphocyte count (ALC), absolute monocyte count (AMC), and lymphocyte to monocyte ratio (LMR) have been used as parameters of systemic inflammation in several tumors. In this study, we evaluated the prognostic significance of preoperative ALC, AMC and LMR in breast cancer and 2000 patients between January 2002 and December 2008 at Sun Yat-Sen University Cancer Center were enrolled. Patients were grouped by the cut-off value according to the receiver operating characteristics (ROC) curve analysis. Kaplan–Meier analysis showed that patients with elevated AMC levels (>0.48 × 109/L) had shorter overall survival (OS, P < 0.001). In multivariate analysis, preoperative AMC was identified as an independent prognostic parameter for OS in breast cancer patients (hazard ratio = 1.374, 95% confidence interval: 1.045–1.807). Subgroup analyses revealed that AMC was an unfavorable prognostic factor in stage II–III breast cancer patients and Luminal B, human epithelial growth factor receptor-2 overexpressing subtype, and triple-negative breast cancer (all P < 0.05). Additionally, the prognostic value of ALC and LMR could not be proven in the current study. Preoperative AMC may serve as an easily available and low-priced parameter to predict the outcomes of breast cancer.
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