Comprehensive analysis of a novel lncRNA profile reveals potential prognostic biomarkers in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the main subtype of malignant kidney cancer. Long non­coding RNA (lncRNA) serves a key role in predicting survival in patients with cancer. The present study aimed to develop an lncRNA­related signature of prognostic values for patients with ccRCC. RNA sequencing data of 454 patients were analyzed from The Cancer Genome Atlas (TCGA). To identify the differentially expressed lncRNAs, the patients from four groups classified by tumor stages were compared. The association between survival outcome and lncRNA expression profile was assessed by the univariate and multivariate Cox proportional hazards model. Survival was analyzed using the log­rank test, and functions of target lncRNAs were investigated through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Finally, 19 lncRNAs were identified as significantly associated with overall survival (OS) time. These lncRNAs were gathered as a signal prognostic signature, which may be a potential biomarker for the prognosis of ccRCC. The risk score was built to evaluate the predictive value of the lncRNA signature. There was a significant positive correlation between ccRCC patients with the low­risk score and OS time (P<0.001). Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was used to verify the result in 17 pairs of ccRCC and adjacent non­tumor tissues. Functional enrichment analysis revealed that these lncRNAs were associated with several molecular pathways of the tumor. The RT­qPCR validation was consistent with the TCGA bioinformatics results. In conclusion, a tumor­specific lncRNA signature of 19 lncRNAs was identified and the joint prognostic power was evaluated in the present study, and this signature was determined to be a potential biomarker for the prognosis of ccRCC.

Selection and Short-Term Outcomes of Living Kidney Donors in Singapore - An Analysis of the Donor Care Registry.

INTRODUCTION: Transplant rates in Singapore have been falling and there is limited information on baseline characteristics and clinical outcomes of living kidney donors nationally. This study aimed to determine the safety of living kidney donor transplant in Singapore by exploring the proportion of donors that meets international selection guidelines and describing short-term clinical outcomes. MATERIALS AND METHODS: We analysed 472 donors who underwent nephrectomies from 1 January 2010 to 31 December 2014 from the Donor Care Registry. We described donor characteristics against 5 international guidelines and measured post-nephrectomy outcomes in 150 local donors for up to 24 months. A multivariate analysis was performed to determine the baseline variables associated with poorer outcomes. RESULTS: There were more foreign than local donors, with differences in gender and hospital types. Selection was generally aligned with international recommendations although 3.0% (using the Chronic Kidney Disease Epidemiology [CKD-EPI] equation) to 8.5% (using radionuclide and creatinine clearance methods) of donors had inappropriate baseline estimated glomerular filtration rates (eGFR) forage. Post-procedure, many foreign donors were lost to follow-up. Over 24 months, eGFR decreased by 33.8% from baseline before recovering gradually to 29.6%. During this period, only 2 donors were admitted for renal or urological conditions and there were no cases of end-stage renal failure or deaths. A lower baseline eGFR (HR: 1.05; 95% Cl, 1.02 to 1.09) and older age (HR: 1.04; 95% Cl, 1.00 to 1.08) were associated with a post-nephrectomy eGFR of less than 60 mL/kg/1.73 m2. CONCLUSION: Kidney donation is safe in Singapore. Donor selection is in keeping with international guidelines and short-term outcomes are comparable to other cohorts.

Integrated analysis of long non-coding RNA­associated ceRNA network reveals potential lncRNA biomarkers in human lung adenocarcinoma.

Accumulating evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor biology. However, the roles of cancer specific lncRNAs in lncRNA-related ceRNA network of lung adenocarcinoma (LUAD) are still unclear. In the present study, the 465 RNA sequencing profiles in LUAD patients were obtained from the cancer genome atlas (TCGA) database, which provides large sample RNA sequencing data free of charge, and 41 cancer specific lncRNAs, 25 miRNAs and 1053 mRNAs (fold change >2, p<0.05) were identified. Then, the lncRNA-miRNA-mRNA ceRNA network of LUAD was constructed with 29 key lncRNAs, 24 miRNAs and 72 mRNAs. Subsequently, we selected these 29 key lncRNAs to analyze their correlation with clinical features, and 21 of them were aberrantly expressed with tumor pathological stage, TNM staging system, lymph node metastasis and patient outcome assessment, respectively. Furthermore, there were 5 lncRNAs (BCRP3, LINC00472, CHIAP2, BMS1P20 and UNQ6494) positively correlated with overall survival (OS, log-rank p<0.05). Finally, 7 cancer specific lncRNAs were randomly selected to verify the expression in 53 newly diagnosed LUAD patients using qRT-PCR. The expression results between TCGA and qRT-PCR were 100% in agreement. The correlation between AFAP1-AS1 and LINC00472 and clinical features were also confirmed. Thus, our results showed the lncRNA expression profiles and we constructed an lncRNA-miRNA-mRNA ceRNA network in LUAD. The present study provides novel insight for better understanding of lncRNA-related ceRNA network in LUAD and facilitates the identification of potential biomarkers for diagnosis and prognosis.

Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer.

Abnormal expression of long non-coding RNAs (lncRNAs) have been shown to play an important role in tumor biology. The Cancer Genome Atlas (TCGA) platform is a large sample sequencing database of lncRNAs, and further analysis of the associations between these data and patients' clinical related information can provide new approaches to find the functions of lncRNA. In the present study, 361 RNA sequencing profiles of gastric cancer (GC) patients were selected from TCGA. Then, we constructed the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network of GC. There were 25 GC specific lncRNAs (fold change >2, p<0.05) identified, 19 of them were included in ceRNA network. Subsequently, we selected these 19 key lncRNAs and analyzed the correlations with clinical features and overall survival, 14 of them were discriminatively expressed with tumor size, tumor grade, TNM stage and lymphatic metastasis (p<0.05). In addition, eight lncRNAs (RPLP0P2, FOXD2-AS1, H19, TINCR, SLC26A4-AS1, SMIM10L2A, SMIM10L2B and SNORD116-4) were found to be significantly associated with overall survival (log-rank p<0.05). Finally, two key lncRNAs HOTAIR and UCA1 were selected for validation of their expression levels in 82 newly diagnosed GC patients by qRT-PCR. Results showed that the fold changes between TCGA and qRT-PCR were 100% in agreement. In addition, we also found that HOTAIR was significantly correlated with tumor size and lymphatic metastasis (p<0.05), and UCA1 was significantly correlated with tumor size, TNM stage and lymphatic metastasis (p<0.05). The clinical relevance of the two lncRNAs and the bioinformatics analysis results were almost the same. Overall, our study showed the GC specific lncRNAs expression patterns and a ceRNA network in GC. Clinical features related to GC specific lncRNAs also suggested these lncRNAs are worthwhile for further study as novel candidate biomarkers for the clinical diagnosis of GC and potential indicators for prognosis.

Changing seroprevalence of hepatitis B virus markers of adults in Singapore.

INTRODUCTION: We presented the findings from 2 seroprevalence studies conducted 6 years apart, so as to determine changes in the hepatitis B surface antigen (HBsAg) positivity rate and immunity to hepatitis B virus (HBV) among Singapore residents aged 18 to 69 years, and to assess the impact of a 4-year catch-up hepatitis B immunisation programme for adolescents and young adults launched in 2001. MATERIALS AND METHODS: Two hepatitis B seroprevalence studies (HBSS) were conducted in 1999 and 2005 based on stored blood samples collected from 4698 participants aged 18 to 69 years during the national health survey (NHS) 1998 and from 3460 participants during the NHS 2004, respectively. Serology for HBsAg, hepatitis B e antigen (HBeAg) and antibody to HBsAg (anti-HBs) were tested by enzyme immunoassay in HBSS 1999 and electrochemiluminescence in HBSS 2005. RESULTS: The overall age-standardised prevalence of HBsAg among Singapore residents aged 18 to 69 years decreased significantly from 4.0% in HBSS 1999 to 2.8% in HBSS 2005 (P = 0.002). The age-standardised prevalence of HBsAg in males (4.9% in 1999) and Chinese (4.7% in 1999) both decreased significantly to 2.7% and 2.8%, respectively in 2005. The overall age-standardised population immunity to HBV (anti-HBs >10 mIU/ml) increased from 39.7% in 1999 to 42.1% in 2005 (P = 0.019). In particular, the age-specific prevalence of anti-HBs showed a significant increase among those in the age group of 18 to 29 years from 27.9% in 1999 to 41.7% in 2005 (P <0.001) and among those in the age group of 30 to 39 years from 39.9% in 1999 to 44.7% in 2005 (P = 0.021). CONCLUSION: There was an overall decline in the HBsAg positivity rate as well as an overall increase in population immunity to HBV. Following the 4-year catch-up immunisation programme, there was a significant increase in the immunity to HBV infection in the younger population aged 18 to 29 years.