Associations between urinary rare Earth elements with renal function: Findings from a cross-sectional study in Guangxi, China.

BACKGROUND: With increased applications of rare earth elements (REEs) across various industries, evaluating the relationship between REEs exposure and potential health effects has become a public concern. In vivo experiments have established that REEs impact renal function. However, relevant epidemiological evidence on this relationship remains scarce. The objective of this study is to examine the impact of exposure to REEs on renal function. METHODS: In this cross-sectional study, 1052 participants were recruited from Guangxi, China. We measured urinary concentrations of 12 REEs using an inductively coupled plasma-mass spectrometer (ICP-MS). Multiple linear regression models were developed to explore the relationship between a single REEs exposure and the estimated glomerular filtration rate (eGFR), a marker of renal function. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to examine the combined effects of REE co-exposure on eGFR. RESULTS: In the multiple linear regression analysis, increasing the concentrations of lanthanum (La, ß: 8.22, 95% CI: 5.67-10.77), cerium (Ce, ß:6.61, 95% CI: 3.80-9.43), praseodymium (Pr, ß: 8.46, 95% CI: 5.85-11.07), neodymium (Nd, ß:8.75, 95% CI: 6.10-11.41), and dysprosium (Dy, ß:7.38, 95% CI: 4.85-9.91) significantly increased the eGFR. In the WQS regression model, the WQS index was significantly associated with eGFR (ß: 4.03, 95% CI: 2.46-5.60), with Pr having the strongest correlation with eGFR. Similar results were obtained in the BKMR model. Additionally, interactions between Pr and La, and Pr and Nd were observed. CONCLUSIONS: Co-exposure to REEs is positively associated with elevated eGFR. Pr is likely to have the most significant influence on increased eGFRs and this might be exacerbated when interacting with La and Nd. Mixed exposure to low doses of REEs had a protective effect on renal function, which can provide some evidence for the exposure threshold of REEs in the environment. TRIAL REGISTRATION: The study has been approved by the Guangxi Medical University Medical Ethics Committee (#20170206-1), and all participants provided written informed consent.

Correlation between urinary rare earth elements and liver function in a Zhuang population aged 35-74 years in Nanning.

BACKGROUND: Animal studies have shown that exposure to REEs can cause severe liver damage, but evidence from population studies is still lacking. Therefore, we investigated the relationship between REEs concentrations in urine and liver function in the population. METHODS: We conducted a cross-sectional study on 1024 participants in Nanning, China. An inductively coupled plasma mass spectrometer (ICP-MS) was used to detect the concentrations of 12 REEs in urine. The relationship between individual exposure to individual REE and liver function was analyzed by multiple linear regression. Finally, the effects of co-exposure to 5 REEs on liver function were assessed by a weighted sum of quartiles (WQS) regression model and a Bayesian kernel machine regression (BKMR) model. RESULTS: The detection rate of 5 REEs, lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), and dysprosium (Dy), is greater than 60%. After multiple factor correction, La, Ce, Pr, Nd, and Dy were positively correlated with serum ALP, Ce, Pr, and Nd were positively correlated with serum AST, while Ce was negatively correlated with serum TBIL and DBIL. Both WQS and BKMR results indicate that the co-exposure of the 5 REEs is positively correlated with serum ALP and AST, while negatively correlated with serum DBIL. There were potential interactions between La and Ce, La and Dy in the association of co-exposure of the 5 REEs with serum ALP. CONCLUSIONS: The co-exposure of the 5 REEs was positively correlated with serum ALP and AST, and negatively correlated with serum DBIL.

Low expression of GOT2 promotes tumor progress and predicts poor prognosis in hepatocellular carcinoma.

Background: To explore the biological function and the underlying mechanisms of GOT2 in hepatocellular carcinoma (HCC). Materials & methods: The expression level and prognostic value of GOT2 were examined using International Cancer Genome Consortium and International Cancer Proteogenome Consortium databases. The cell counting kit-8 method, clone formation, Transwell® assays and western blotting were used to evaluate the effects of GOT2 on the biological function and autophagy of HCC cells. Results: The expression of GOT2 was downregulated in HCC tissues and correlated with poor prognosis of HCC patients. Knockdown of GOT2 promoted proliferation, migration and invasion of HCC cells and promoted cells' proliferation by inducing autophagy. Conclusion: GOT2 plays a tumor-inhibitory role in HCC and may be a potential therapeutic target for HCC.

Associations between maternal serum phytoestrogens and liver function markers: a cross-sectional study from China.

Phytoestrogens (PEs) may harm liver function. However, studies in pregnant women are limited. Our study was conducted in pregnant women to assess the effect of serum PEs on liver function markers. We conducted a cross-sectional study focusing in the first trimester of pregnancy. A total of 352 pregnant women were enrolled in the study. We used generalized linear model (GLM) to explore the associations between each PE and each marker of liver function. We used Quantile g-computation (Qgcomp) and Bayesian kernel machine regression (BKMR) models to explore the associations between mixed exposure to all PEs and liver function markers. The GLM results showed that equol (EQU), daidzein (DAD), genistein (GEN), enterolactone (ENT), and enterodiol (END) were negatively correlated with albumin (ALB). DAD and GEN were associated with elevated alanine aminotransferase (ALT). DAD, GEN, naringin (NAR), and glycitein (GLY) were related to elevated aspartate aminotransferase (AST). Mixed exposure model results showed that the mixture of PEs was associated with reduced ALB. Our results support the existence of associations between PEs and maternal liver function in the first trimester. Emphasizing the detrimental associations between serum PEs and liver function in pregnant women is essential to ensure maternal liver health during pregnancy.

Comprehensive investigation of the prognostic values and molecular mechanisms of syntaxin binding protein 5 antisense RNA 1 in patients with colon adenocarcinoma based on RNA sequencing dataset.

Objective: The main purpose of this study is to perform a comprehensive investigation of the prognostic value and molecular mechanism of syntaxin binding protein 5 antisense RNA 1 (STXBP5-AS1) through the whole genome RNA sequencing data of the The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) cohort. Methods: There were 438 COAD patients were fit into current study for survival analysis. Gene expression profiling interactive analysis 2.0, Database for Annotation, Visualization and Integrated Discovery v6.8, gene set enrichment analysis (GSEA) and connectivity map (CMap) are used to investigate the molecular mechanisms and targeted drugs of STXBP5-AS1 in COAD. Results: By comparing the expression level of tumor and non-tumor tissues, we found that STXBP5-AS1 was notablely down-regulated in COAD tumor tissues. Survival analysis suggested that low STXBP5-AS1 expression was significantly related to poor overall survival (OS) of COAD (log-rank P=0.035, adjusted P=0.005, HR=0.545, 95%CI=0.356-0.836). The enrichment analysis of STXBP5-AS1 co-expressed genes, GSEA and differentially expressed genes suggests that STXBP5-AS1 may play a part in COAD by regulating the following biological processes or pathways: cell junction, DNA replication, apoptosis, cell cycle, metastasis, tumor protein 53, Wnt, mTORC1, MCM, notch receptor 4, transforming growth factor beta receptor, and cGMP-PKG signaling pathway. CMap analysis was screened out four small molecule drugs (anisomycin, cephaeline, NU-1025 and quipazine) that may be used as STXBP5-AS1 targeted therapy drugs in COAD. The co-expression analysis of STXBP5-AS1 and immune cell gene signature indicated that STXBP5-AS1 was significantly related to immune cell gene set in normal intestinal tissues, but not in COAD tumor tissues. Conclusion: Our results revealed that STXBP5-AS1 is notablely down-regulated in COAD tumor tissues, and may act as a novel prognostic biomarker for COAD.

Clinical significance and biological mechanisms of glutathione S-transferase mu gene family in colon adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) is the most common form of colon cancer. The glutathione S-transferase Mu (GSTM) gene belongs to the GST gene family, which functions in cell metabolism and detoxification. The relationship between GSTM and COAD and the underlying mechanism remain unknown. METHODS: Data extracted from The Cancer Genome Atlas included mRNA expression and clinical information such as gender, age, and tumor stage. Prognostic values of GSTM genes were identified by survival analysis. Function and mechanism of prognostic GSTM genes were identified by gene set enrichment analysis. A nomogram was used to predict the contribution of risk factors to the outcome of COAD patients. RESULTS: Low expression of GSTM1 and GSTM2 was related to favorable OS (adjusted P = 0.006, adjusted HR = 0.559, 95% CI = 0.367-0.849 and adjusted P = 0.002, adjusted HR = 0.519, 95% CI = 0.342-0.790, respectively) after adjusting for tumor stage. Enrichment analysis also showed that genes involved were related to cell cycle, metabolism, and detoxification processes, as well as the Wnt signaling and NF-κB pathways. CONCLUSIONS: In conclusion, low expression of GSTM1 and GSTM2 were significantly associated with favorable prognosis in COAD. These two genes may serve as potential biomarkers of COAD prognosis.

Big Data-Based Identification of Multi-Gene Prognostic Signatures in Liver Cancer.

Simultaneous identification of multiple single genes and multi-gene prognostic signatures with higher efficacy in liver cancer has rarely been reported. Here, 1,173 genes potentially related to the liver cancer prognosis were mined with Coremine, and the gene expression and survival data in 370 samples for overall survival (OS) and 319 samples for disease-free survival (DFS) were retrieved from The Cancer Genome Atlas. Numerous survival analyses results revealed that 39 genes and 28 genes significantly associated with DFS and OS in liver cancer, including 18 and 12 novel genes that have not been systematically reported in relation to the liver cancer prognosis, respectively. Next, totally 9,139 three-gene combinations (including 816 constructed by 18 novel genes) for predicting DFS and 3,276 three-gene combinations (including 220 constructed by 12 novel genes) for predicting OS were constructed based on the above genes, and the top 15 of these four parts three-gene combinations were selected and shown. Moreover, a huge difference between high and low expression group of these three-gene combination was detected, with median survival difference of DFS up to 65.01 months, and of OS up to 83.57 months. The high or low expression group of these three-gene combinations can predict the longest prognosis of DFS and OS is 71.91 months and 102.66 months, and the shortest is 6.24 months and 13.96 months. Quantitative real-time polymerase chain reaction and immunohistochemistry reconfirmed that three genes F2, GOT2, and TRPV1 contained in one of the above combinations, are significantly dysregulated in liver cancer tissues, low expression of F2, GOT2, and TRPV1 is associated with poor prognosis in liver cancer. Overall, we discovered a few novel single genes and multi-gene combinations biomarkers that are closely related to the long-term prognosis of liver cancer, and they can be potential therapeutic targets for liver cancer.

Genome­scale analysis to identify potential prognostic microRNA biomarkers for predicting overall survival in patients with colon adenocarcinoma.

The aim of the present study was to identify potential prognostic microRNA (miRNA) biomarkers for colon adenocarcinoma (COAD) prognostic prediction using the dataset of The Cancer Genome Atlas (TCGA). The genome­wide miRNA sequencing dataset and corresponding COAD clinical information were downloaded from TCGA. Prognosis­related miRNA screening was performed by genome­wide multivariable Cox regression analysis and used for prognostic signature construction. Ten miRNAs (hsa­mir­891a, hsa­mir­6854, hsa­mir­216a, hsa­mir­378d­1, hsa­mir­92a­1, hsa­mir­4709, hsa­mir­92a­2, hsa­mir­210, hsa­mir­940 and hsa­mir­887) were identified as prognostic miRNAs and used for further prognostic signature construction. The 10­miRNA prognostic signature showed good performance in prognosis prediction (adjusted P<0.0001; adjusted hazard ratio, 4.580; 95% confidence interval, 2.783­7.538). In the time­dependent receiver operating characteristic analysis, the area under the curve was 0.735, 0.788, 0.806, 0.806, 0.775 and 0.900 for 1­, 2­, 3­, 4­, 5­ and 10­year COAD overall survival prediction, respectively. Comprehensive survival analysis suggested that the 10­miRNA prognostic signature is an independent prognostic factor in COAD, with a better performance in COAD overall survival prediction than other traditional clinical parameters. Functional enrichment indicated that the corresponding target genes were significantly enriched in multiple biological processes and pathways, including regulation of cell proliferation, cell cycle, cell growth, and Wnt and transforming growth factor­ß signaling pathways. In conclusion, our present study identified a 10­miRNA expression signature that may serve as a potential prognostic biomarker in COAD patients.

Prognostic value of alcohol dehydrogenase mRNA expression in gastric cancer.

Previous studies have reported that alcohol dehydrogenase (ADH) isoenzymes possess diagnostic value in gastric cancer (GC). However, the prognostic value of ADH isoenzymes in GC remains unclear. The aim of the present study was to identify the prognostic value of ADH genes in patients with GC. The prognostic value of ADH genes was investigated in patients with GC using the Kaplan-Meier plotter tool. Kaplan-Meier plots were used to assess the difference between groups of patients with GC with different prognoses. Hazard ratios (HR) and 95% confidence intervals (CI) were used to assess the relative risk of GC survival. Overall, 593 patients with GC and 7 ADH genes were included in the survival analysis. High expression of ADH 1A (class 1), α polypeptide (ADH1A; log-rank P=0.043; HR=0.79; 95% CI: 0.64-0.99), ADH 1B (class 1), ß polypeptide (ADH1B; log-rank P=1.9×10-05; HR=0.65; 95% CI: 0.53-0.79) and ADH 5 (class III), χ polypeptide (ADH5; log-rank P=0.0011; HR=0.73; 95% CI: 0.6-0.88) resulted in a significantly decreased risk of mortality in all patients with GC compared with patients with low expression of those genes. Furthermore, protective effects may additionally be observed in patients with intestinal-type GC with high expression of ADH1B (log-rank P=0.031; HR=0.64; 95% CI: 0.43-0.96) and patients with diffuse-type GC with high expression of ADH1A (log-rank P=0.014; HR=0.51; 95% CI: 0.3-0.88), ADH1B (log-rank P=0.04; HR=0.53; 95% CI: 0.29-0.98), ADH 4 (class II), π polypeptide (log-rank P=0.033; HR=0.58; 95% CI: 0.35-0.96) and ADH 6 (class V) (log-rank P=0.037; HR=0.59; 95% CI: 0.35-0.97) resulting in a significantly decreased risk of mortality compared with patients with low expression of those genes. In contrast, patients with diffuse-type GC with high expression of ADH5 (log-rank P=0.044; HR=1.66; 95% CI: 1.01-2.74) were significantly correlated with a poor prognosis. The results of the present study suggest that ADH1A and ADH1B may be potential prognostic biomarkers of GC, whereas the prognostic value of other ADH genes requires further investigation.

Prognostic and clinical significance of syndecan-1 in colorectal cancer: a meta-analysis.

BACKGROUND: Syndecan-1 plays a vital role in the suppression, transformation, and migration of several cancer types, including colorectal cancer (CRC). However, the prognostic and clinical significance of syndecan-1 in CRC remains conflicting. Therefore, we performed a meta-analysis to clarify this relationship. METHODS: A comprehensive literature search for relevant studies published up to December 2014 was performed using PubMed, EMBASE, and Ovid library database. The odds ratio (OR) and pooled hazard ratio (HR) with their 95 % confidence intervals (CI) were used to estimate the effects. RESULTS: Ten studies with 888 CRC patients were selected for evaluation. The results showed that syndecan-1 expression was lower in CRC tissue than in normal colorectal tissue (OR = 0.02, 95 % CI = 0.00-0.09), and lower in the advanced stage than in the early stage (OR = 2.24, 95 % CI = 1.14 - 4.42). Additionally, syndecan-1 expression was higher in well and moderately differentiated CRC than in poorly differentiated CRC (OR = 2.91, 95 % CI = 1.21-6.98); no significant difference was found in patients with or without lymph node metastasis (OR = 0.91, 95 % CI = 0.34-2.43) and distant metastasis (OR = 0.89, 95 % CI = 0.19-4.21). The pooled results showed that syndecan-1 expression was not associated with survival in CRC patients (HR = 0.93, 95 % CI = 0.86-1.01). CONCLUSION: This meta-analysis indicated that loss of syndecan-1 expression is associated with CRC development, histological differentiation, and clinical stage, but not with lymph node metastasis and distant metastasis. In addition, these findings fail to support the prognostic significance of syndecan-1 in CRC.