BackgroundAfter surgical resection of hepatocellular carcinoma (HCC), recurrence is common, especially in patients presenting with vascular invasion or multifocal disease after curative surgery. Consequently, we examined the expression pattern and prognostic value of miR-19b in samples from these patients.MethodsWe performed a miRNA microarray to detect differential expression of microRNAs (miRNAs) in 5 paired samples of HCC and non-tumoral adjacent liver tissue and a quantitative real-time polymerase chain reaction (PCR) analysis to validate the results in 81 paired samples of HCC and adjacent non-tumoral liver tissues. We examined the associations of miR-19b expression with clinicopathological parameters and survival. MiR-19b was knocked down in Hep3B and an mRNA microarray was performed to detect the affected genes.ResultsIn both the miRNA microarray and real-time PCR, miR-19b was significantly overexpressed in the HCC tumor compared with adjacent non-tumor liver tissues (P < 0.001). The expression of miR-19b was significantly higher in patients who were disease-free 2 years after surgery (P < 0.001). High miR-19b expression levels were associated with higher α-fetoprotein levels (P = 0.017). In the log-rank test, high miR-19b was associated with better disease-free survival (median survival 37.107 vs. 11.357; P = 0.022). In Cox multivariate analysis, high miR-19b predicted better disease-free survival and overall survival (hazards ratio [HR] = 0.453, 95 % confidence interval [CI] = 0.245–0.845, P = 0.013; HR = 0.318, CI = 0.120–0.846, P = 0.022, respectively). N-myc downstream regulated 1 (NDRG1) was downregulated, while epithelial cell adhesion molecule (EPCAM), hypoxia-inducible factor 1-alpha (HIF1A), high-mobility group protein B2 (HMGB2), and mitogen activated protein kinase 14 (MAPK14) were upregulated when miR-19b was knocked down in Hep3B.ConclusionsThe overexpression of miR-19b was significantly correlated with better disease-free and overall survival in patients with HCC presenting with vascular invasion or multifocal disease after curative surgery. MiR-19b may influence the expression of NDRG1, EPCAM, HMGB2, HIF1A, and MAPK14.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1671-5) contains supplementary material, which is available to authorized users.
BackgroundThe contribution of human immunodeficiency virus (HIV) co-infection to tuberculosis (TB) recurrence is well established worldwide. We conducted this study to investigate associated factors for recurrent TB in Taiwan, which has a relatively low prevalence of HIV.MethodsA case-control study nested within a nationwide population-based cohort was performed using the Taiwan National Health Insurance (NHI) database from 1998 to 2010. Patients with notified TB were identified according to diagnosis codes and prescriptions of anti-TB drugs for more than 60 days. Recurrent TB was defined as cases being retreated for more than 60 days and 6 months after the end of previous TB episode. Four controls were randomly selected from cohort and matched to each case by observational period within a calendar year. Socio-demographic variables and comorbidities were evaluated as factors associated with TB recurrence.ResultsThere were totally 760 patients being investigated (608 controls and 152 cases). During an average 5.12 years of follow-up, 3.76% of all developed recurrent TB and the incidence of TB recurrence was 734 per 100,000 person-years. About half of recurrence (55%) was notified within three years of follow-up, and most (86%) recurrences were intrapulmonary. Independent associated factors for TB recurrence included: male (odds ratio, OR: 2.23, 95% confidence interval, CI: 1.40–3.53), diabetes mellitus (DM) (OR: 1.51, 95% CI: 1.02–2.13), chronic obstructive pulmonary disease (COPD) (OR: 1.59, 95% CI: 1.08–2.36) and lower socio-economic status (p=0.001 between groups).ConclusionsDespite low prevalence of HIV in the Taiwanese population, the incidence of recurrent TB among Taiwanese was not less than that of other countries. Identification of subgroups such as male gender, low economic status, DM and COPD should be a high priority in TB control programs.
Occupational lung diseases are well recognized risk factors for tuberculosis (TB). However, little research investigated the effect of TB on the clinical course and outcome of occupational lung diseases.We conducted a 13-year observational study of a nationwide cohort to evaluate the risk and prognosis of TB among patients with occupational lung diseases in Taiwan.By using the Taiwan National Health Insurance database, occupational lung diseases cohort was identified according to diagnosis codes from 1998 to 2008 and prospectively monitored until the end of 2010, loss to follow-up, or death. Newly diagnosed TB, comorbidities, and demographic characteristics were evaluated as prognostic variables in the survival analysis of patients with occupational lung diseases using Cox proportional hazard regression models.A total of 12,787 study participants were enrolled with an average of 9.69 years of follow-up. Among them, 586 (4.58%) had newly diagnosed TB and 3180 (24.87%) died during follow-up. The incidence of TB was 473 per 100,000 person-years, and the risk of TB infection significantly increased over time. The independent risk factors for mortality included male gender (hazard ratio [HR]: 2.23, 95% confidence interval [CI]: 1.91–2.60), age (HR: 1.05, 95% CI: 1.05–1.06), TB (HR: 1.17, 95% CI: 1.01–1.37), congestive heart failure (HR: 1.44, 95% CI: 1.17–1.79), cerebrovascular disease (HR: 1.34, 95% CI: 1.15–1.57), chronic obstructive pulmonary disease (HR: 1.44, 95% CI: 1.33–1.56), and asthma (HR: 1.27, 95% CI: 1.15–1.40). In addition, patients with TB infections had worse outcomes in the survival analysis than those without TB (log-rank test P = 0.02).Despite the low prevalence of occupational lung diseases in Taiwan, patients with those diseases had a higher TB incidence than the general population did (473 vs 55 per 100,000 person-years). Furthermore, even with effective antimicrobial chemotherapy, TB infection was a prognostic factor leading to poor outcomes in the patients with occupational lung diseases. We recommend intensive medical surveillance of TB in these high-risk patients for better control of TB and improvement of occupational health in Taiwan.
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