O-linked-ß-N-acetylglucosamine (O-GlcNAc) modification is a crucial post-translational modification. The enzymes responsible for the addition and removal of O-GlcNAc have been identified as O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). In this study, O-GlcNAcylation level was examined in forty hepatocellular carcinoma (HCC) tissues of patients who underwent liver transplantation (LT) and ten healthy liver tissues by immunohistochemistry analysis. We also examined the expression of OGT and OGA in sixty HCC samples using real-time reverse-transcription polymerase chain reaction and analyzed their correlations with clinical parameters and prognosis in sixty HCC patients treated with LT. Additionally, the global O-GlcNAcylation level was altered through OGT and OGA silencing in the HCC cell line, and the effects of O-GlcNAcylation on cancer malignancy were investigated. We found that the global O-GlcNAcylation levels were significantly elevated in HCC tissues than that in healthy liver tissues (P = 0.031); moreover, O-GlcNAcylation was significantly enhanced in the tumor tissues of patients who had suffered from HCC recurrence after LT compared with those who had not (P = 0.046). Importantly, low expression of OGA was an independent prognostic factor for predicting tumor recurrence of HCC following LT (P = 0.041, hazard ratio, 0.438), especially in AFP low patients. In vitro assays demonstrated that O-GlcNAcylation play important roles in migration, invasion, and viability of HCC cells, partly through regulating E-cadherin, MMP1, MMP2, and MMP3 expression. Altogether, these results suggest that O-GlcNAcylation might play important roles in HCC formation and progression and may be a potential marker to predict patient risk of recurrence after LT and a valuable target for therapy.

Breast cancer (BC) is the most common female malignancy within the spectrum of human cancer. One promising way to reduce the mortality and morbidity of BC is to explore novel diagnostic markers for early diagnosis and prognostication. The neutrophil lymphocyte ratio (NLR) is a good reflection of inflammation, which plays an important role in tumor progression and metastasis. However, the association between NLR and BC prognosis remains unclear. The aim of this meta-analysis is to explore the prognostic value of NLR in BC. Among the screened references in the database, 12 eligible studies were identified in this study. Patients with a higher NLR had a shorter disease-free survival (hazard ratio =1.46, 95% confidence interval: 1.12–1.90, P=0.044) and overall survival (hazard ratio =2.03, 95% confidence interval: 1.41–2.93, P<0.001). In the subgroup analysis of NLR and disease-free survival, the studies from Eastern countries had a positive result with perfect homogeneity (I2=0); however, this homogeneity has not been achieved in studies from Western countries. In the subgroup analysis of the NLR and overall survival, the results of the univariate and multivariate analyses were completely different, with different heterogeneity. In the luminal A and luminal B subtypes, we found that there was no association between the NLR and overall survival in the BC patients. Positive results were obtained in the analyses of the human epidermal growth factor receptor 2 (HER2)-positive and triple-negative BC subtypes. In conclusion, this meta-analysis suggests that NLR is a good prognostic marker for BC, and patients with a higher NLR have poorer prognoses. Future studies should perform more detailed investigations to decrease heterogeneity and determine the appropriate cut-off values for different races.

BackgroundIncreasing evidence indicates that deregulation of microRNAs (miRNAs) is involved in tumorigenesis. Downregulation of microRNA-503 has been observed in various types of diseases, including cancer. However, the biological function of miR-503 in hepatocellular carcinoma (HCC) is still largely unknown. In this study we aimed to elucidate the prognostic implications of miR-503 in HCC and its pathophysiologic role.MethodsQuantitative reverse transcriptase polymerase chain reaction was used to evaluate miR-503 expression in HCC tissues and cell lines. Western blotting was performed to evaluate the expression of the miR-503 target genes. In vivo and in vitro assays were performed to evaluate the function of miR-503 in HCC. Luciferase reporter assay was employed to validate the miR-503 target genes.ResultsmiR-503 was frequently downregulated in HCC cell lines and tissues. Low expression levels of miR-503 were associated with enhanced malignant potential such as portal vein tumor thrombi, histologic grade, TNM stage, AFP level and poor prognosis. Multivariate analysis indicated that miR-503 downregulation was significantly associated with worse overall survival of HCC patients. Functional studies showed miR-503 suppressed the proliferation of HCC cells by induction of G1 phase arrest through Rb-E2F signaling pathways, and thus may function as a tumor suppressor. Further investigation characterized two cell cycle-related molecules, cyclin D3 and E2F3, as the direct miR-503 targets.ConclusionOur data highlight an important role for miR-503 in cell cycle regulation and in the molecular etiology of HCC, and implicate the potential application of miR-503 in prognosis prediction and miRNA-based HCC therapy.