MicroRNAs play an important role in liver cancer genesis and progression. In this study, we identified down-regulation of miR-146b-5p associated with tumor growth, metastasis and poor survival in hepatocellular carcinoma (HCC) patients. miR-146b-5p could suppress proliferation, migration, and invasion and induced apoptosis in vitro and in vivo. Remarkably, TNF receptor associated factor 6 (TRAF6) was confirmed as a direct target of miR-146b-5p in HCC and miR-146b-5p exerted the tumor suppression roles through inhibiting the phosphorylation of Akt mediated by TRAF6. Furthermore, we identified long non-coding RNA MALAT1 as a molecular sponge of miR-146b-5p to down-regulate its expression in HCC. In general, our results indicate that miR-146b-5p inhibits tumor growth and metastasis of HCC by targeting TRAF6 mediated Akt phosphorylation.

Thrombocytopenia has been acknowledged to be a crucial risk factor for cirrhosis formation and hepatocarcinogenesis in chronic liver diseases. However, to date, the association between platelet count (PLT) and the prognosis of hepatocellular carcinoma (HCC) remains inconsistent and controversial.The aim of the present study was to determine whether PLT could be used as a useful predictor of survival in patients with HCC.We performed systematic review in online databases, including PubMed, EmBase, and Web of Science, from inception until 2014. Studies were included if a statistical relationship was investigated between PLT and survival for HCC, and hazard ratio (HR) and 95% confidence intervals (CIs) for overall survival (OS) or recurrence-free survival (RFS) were provided. The quality of each included study was assessed by Newcastle–Ottawa scale score. To synthesize these studies, a random-effects model or a fixed-effects model was applied as appropriate. Then, we calculated heterogeneity, performed sensitivity analysis, tested publication bias, and did subgrouped and meta-regression analysis.Finally, we identified 33 eligible articles (published from 1998 to 2014) involved 5545 patients by retrieval. A low level of preoperative PLT was found to be significantly associated with a poor survival of HCC. Irrespective of the therapy used, the pooled HRs for OS and RFS were 1.41 (95% CI, 1.14–1.75) and 1.44 (95% CI, 1.13–1.83), respectively. Specifically, in patients who underwent liver resection, the pooled HRs for OS and RFS were 1.67 (95% CI, 1.22–2.27) and 1.44 (95% CI, 1.04–1.99), respectively. Furthermore, patients with preoperative thrombocytopenia (PLT < 100 × 109/L) had a worse OS (HR: 1.73, 95% CI, 1.29–2.32) and RFS (HR: 1.57, 95% CI, 1.31–1.87) in comparison with patients without thrombocytopenia. All our findings showed no significant changes due to the removal of any study or the use of an opposite-effects model, and there was no significant publication bias. The limitations of this meat-analysis were nonuniform cut-off values of PLT, high between-study heterogeneities, potential confounders, and a bias of publication year.A low preoperative PLT level results in an unfavorable outcome in HCC. PLT is a simple, inexpensive, and useful predictor of survival in patients with HCC.

Pancreatic cancer (PC) is a highly fatal disease worldwide and is often misdiagnosed in its early stages. The exploration of novel non-invasive biomarkers will definitely benefit PC patients. Recently, circulating miRNAs in body fluids are emerging as non-invasive biomarkers for PC diagnosis. In this study, we first conducted comprehensive robust rank aggregation (RRA) analysis based on 21 published miRome profiling studies. We statistically identified and clinically validated a miRNA expression pattern in PC patients. These miRNAs consisted of four up-regulated (hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-210-3p and hsa-miR-155-5p) and three down-regulated miRNAs (hsa-miR-217, hsa-miR-148a-3p and hsa-miR-375). Among them, hsa-miR-21-5p was one of the most highly expressed miRNAs in the serum of PC patients. Our validation test further suggested a relatively high accuracy of serum hsa-miR-21-5p levels in the diagnosis of PC, with a sensitivity of 0.77 and a specificity of 0.80. Finally, a diagnostic meta-analysis based on 9 studies also revealed favorable sensitivity and specificity of circulating hsa-miR-21-5p for the diagnosis of PC (pooled sensitivity and specificity were 0.76 and 0.74, respectively), which was consistent with our findings. Taken together, as one of the most aberrantly expressed miRNAs in PC, circulating hsa-miR-21-5p might be a promising serum biomarker in patients with PC.

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BackgroundPretreatment nutritional and immunological statuses play an indispensable role in predicting the outcome of patients with various types of malignancies. The purpose of this study is to evaluate the predictive value of albumin/globulin ratio (AGR) in overall survival (OS) and recurrence in patients with hepatocellular carcinoma (HCC) following radical hepatic carcinectomy.Patients and methodsThis retrospective study included a total of 172 patients with HCC with complete medical and follow-up information between 2002 and 2012. AGR was calculated according to the following formula: AGR = albumin/globulin. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff value. The associations of AGR with clinicopathological characteristics and prognosis were assessed. Further multivariate analysis using Cox regression model and subgroup analysis was performed to evaluate the predictive value.ResultsReceiver operating characteristic curve determined 37.65, 31.99, and 1.48 as the optimal cutoff values of albumin, globulin, and AGR in terms of 5-year OS or death, respectively. On the basis of the cutoff value of AGR, all the patients were divided, respectively, into low-AGR (n=105) and high-AGR (n=67) groups. AGR was found to be significantly correlated with age, cancer embolus, international normalized ratio, and postoperative outcome (P<0.05). Hepatitis B virus infection (hazard ratio [HR]: 2.125; 95% confidence interval [CI]: 1.285–3.153), tumor node metastasis stage (HR: 1.656; 95% CI: 1.234–2.223), serum albumin (HR: 0.546; 95% CI: 0.347–0.857), and AGR (HR: 0.402; 95% CI: 0.233–0.691) were independent predictors of OS via univariate and multivariate survival analyses. However, alpha-fetoprotein (HR: 1.708; 95% CI: 1.027–2.838), tumor node metastasis stage (HR: 1.464; 95% CI: 1.078–1.989), and AGR (HR: 0.493; 95% CI: 0.293–0.828) functioned as independent risk variables for predicting recurrence. Moreover, AGR showed superior prognostic value for OS and recurrence in the subgroups with normal level of albumin or survival time beyond 6 months.ConclusionPretreatment AGR might serve as an effective biomarker to evaluate the prognosis of patients with a diagnosis of HCC. Based on the results, AGR, characterized with easy accessibility, objectivity, and noninvasiveness, should be included in the routine assessment of HCC.

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Background Thyroid cancer is a growing threat to human health. Few studies have explored trends of thyroid cancer and relationships with social development factors. In this study, we explored the trend and relationship based on GBD. Methods By using GBD study, we obtained detailed data of thyroid cancer. Incidence, mortality and DALY were used to assess epidemiological characteristics. ASR and EAPC were used to estimate the trend. Results Globally, the incidence significantly increased from 1990 to 2017, especially in high‐income regions. Males and middle SDI region demonstrated a higher increase of age‐standardized incidence rates. Unlike incidence trend, mortality trend showed a minor increase, and even showed a decreasing trend in some regions such as Eastern Sub‐Saharan Africa. Additionally, the DALY trend also demonstrated a slightly increase with an EAPC of 0.77 (95% CI 0.73–0.81). More significant increase of DALY was found in males, middle SDI region and high‐income Asia Pacific. The incidence of thyroid cancer peaked in middle‐aged people, while the mortality and DALY peaked in elder‐aged. Moreover, the proportion of thyroid cancer deaths contributable to high BMI was highest in developed countries and middle‐aged people. Conclusions Thyroid cancer is a public health problem worldwide. Over‐diagnosis might be partly responsible for its rising trend. It remains us to revise the guidelines to avoid unnecessary burdens. Moreover, we should pay attention to the risk factors of thyroid cancer. More targeted measures should be formulated to improve potential environmental and lifestyle‐related factors which might contribute to rising trend of thyroid cancer.