BackgroundMetastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) has been demonstrated to be an important player in various human malignancies; it is thought to promote tumor growth by cell cycle regulating. However, the roles of MALAT1 in esophageal squamous cell carcinoma(ESCC), and the mechanisms involved in cell cycle regulation remain poorly understood. Moreover, the factors contributing to its up-regulation in tumor tissues are still largely unclear.MethodsExpression of MALAT1 was determined from cell lines and clinical samples by qRT-PCR. The effects of MALAT1 knockdown on cell proliferation, cell cycle, apoptosis, migration, and invasion were evaluated by in vitro and in vivo assays. The potential protein expression changes were investigated by Western-blotting. The methylation status of the CpG island in the MALAT1 promoter was explored by bisulfite sequencing, while the copy numbers in tumor tissues and blood samples were detected by a well-established AccuCopyTM method.ResultsMALAT1 was over-expressed in 46.3% of ESCC tissues, mostly in the high-stage tumor samples. Enhanced MALAT1 expression levels were positively correlated with clinical stages, primary tumor size, and lymph node metastasis. Inhibition of MALAT1 suppressed tumor proliferation in vitro and in vivo, as well as the migratory and invasive capacity. MALAT1 depletion also induced G2/M phase arrest and increased the percentage of apoptotic cells. Western-blotting results implicated that the ATM-CHK2 pathway which is associated with G2/M arrest was phosphorylated by MALAT1 knockdown. No effects of CpG island methylation status on MALAT1 expression were found, whereas amplification of MALAT1 was found in 22.2% of tumor tissues, which correlated significantly with its over-expression. However, neither association between tissue copy number amplification and germline copy number variation, nor correlation between germline copy number variation and ESCC risk were identified in the case–control study.ConclusionsOur data suggest that MALAT1 serves as an oncogene in ESCC, and it regulates ESCC growth by modifying the ATM-CHK2 pathway. Moreover, amplification of MALAT1 in tumor tissues may play an important role for its up-regulation, and it seems that the gene amplification in tumor tissues emerges during ESCC progression, but is not derived from germline origins.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0123-z) contains supplementary material, which is available to authorized users.
Our study indicated that a high lymphocyte to monocyte ratio might be a useful marker for colorectal cancer prognosis. As most of these findings were from retrospective studies, further studies are needed to verify the significance of the lymphocyte to monocyte ratio in clinical practice.
Many studies have been reported that platelet–lymphocyte ratio (PLR) may be associated with the prognosis of colorectal cancer (CRC), but the results are inconsistent. Current opinion on the prognostic role of the PLR in CRC is inconsistent and inconclusive. Therefore, we conduct a meta-analysis that combines these studies and to identify the prognostic value of PLR in patients with CRC. Data were retrieved from PubMed, EMBASE, Cochrane Library, and Web of Science databases that came from inception through January 2016. We extracted data from the characteristics of each study and analyzed the relationship between PLR and overall survival (OS), disease-free survival (DFS), or other prognosis in patients with CRC by using the hazard ratio (HR) and 95% confidence intervals (95% CIs). Of the 256 identified studies, 15 studies were included and a total of 3991 patients were included. In a meta-analysis, patients with an elevated PLR had a significantly lower OS (pooled HR, 1.53; 95% CI, 1.24–1.89; P ≤ 0.001), DFS (pooled HR, 1.68; 95% CI, 1.07–2.62; P = 0.023). Even after sensitivity analyses and trim and fill method, high PLR remains significantly predictive poorer OS, but not DFS. In addition, our meta-analysis indicated that increased PLR is also significantly associated with the poor tumor differentiation [odds ratio (OR) 2.12; 95% CI, 1.45–3.08, P < 0.001)], the propensity toward depth of infiltration (OR 1.69; 95% CI, 1.20–2.39, P = 0.003), and recurrence in patients with CRC (HR, 2.71; 95% CI, 1.31–5.60, P = 0.005). This meta-analysis suggested that a high peripheral blood PLR can be used as a predictor of OS connected with clinicopathological parameters in patients with CRC, not DFS. These ratios may thus contribute to inform more personalized treatment decisions and predict treatment outcomes.
Increasing evidence indicates that the neutrophil to lymphocyte ratio (NLR) is a useful biomarker of long-term outcomes in patients with cholangiocarcinoma. However, the prognostic role of NLR in patients with cholangiocarcinoma remains unclear. Thus, the current meta-analysis was undertaken to clarify the correlation between NLR and overall survival (OS) in cholangiocarcinoma, and a comprehensive literature research was conducted to understand the association of NLR and prognosis of cholangiocarcinoma. The hazard ratio (HR) with 95% confidence interval (CI) was used to assess OS. The synthesized HR of 1.449 (95% CI: 1.296–1.619, P < 0.001) indicated that a high NLR had an unfavourable effect on OS. Overall, this meta-analysis suggested that elevated preoperative NLR is associated with poorer rates of survival in cholangiocarcinoma patients.
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