Evaluation of graphical models for multi-group metabolomics data.

Gaussian graphical model is a strong tool for identifying interactions from metabolomics data based on conditional correlation. However, data may be collected from different stages or subgroups of subjects with heterogeneity or hierarchical structure. There are different integrating strategies of graphical models for multi-group data proposed by data scientists. It is challenging to select the methods for metabolism data analysis. This study aimed to evaluate the performance of several different integrating graphical models for multi-group data and provide support for the choice of strategy for similar characteristic data. We compared the performance of seven methods in estimating graph structures through simulation study. We also applied all the methods in breast cancer metabolomics data grouped by stages to illustrate the real data application. The method of Shaddox et al. achieved the highest average area under the receiver operating characteristic curve and area under the precision-recall curve across most scenarios, and it was the only approach with all indicators ranked at the top. Nevertheless, it also cost the most time in all settings. Stochastic search structure learning tends to result in estimates that focus on the precision of identified edges, while BEAM, hierarchical Bayesian approach and birth-death Markov chain Monte Carlo may identify more potential edges. In the real metabolomics data analysis from three stages of breast cancer patients, results were in line with that in simulation study.

Dysregulated N6-methyladenosine methylation writer METTL3 contributes to the proliferation and migration of gastric cancer.

Accumulating evidence implies that N6-methyladenosine (m6A) methylation participated in the tumorigenesis of gastric cancer (GC). Here we synthetically analyzing the prognostic value and expression profile of seven m6A methylation-relevant genes through silico analysis of sequencing data downloaded from The Cancer Genome Atlas, Kaplan-Meier plotter, and Gene Expression Omnibus database. We explored the methyltransferase-like 3 (METTL3) expression in GC cell line and tumor tissues by reverse transcription quantitative polymerase chain reaction and western blot analysis. The m6A methylation status of total RNA was measured by m6A RNA methylation quantification kit. Small interfering RNA was used to establish METTL3 knockdown cell lines. We also measure the proliferation and migration capability GC cell. Furthermore, we detect the epithelial cell mesenchymal transition marker and m6A methylation level after METTL3 knock down. Our result revealed that METTL3 was significantly increased in GC tissues compared with control in big crowd data sets. Survival analysis showed that METTL3 serve as a poor prognostic factor for GC patients. The expression level of METTL3 gradually increased with the progress of tumor stage and grade. GFI1 is an important transcription factor associated with METTL3. We verified the up-trend of METTL3 in messenger RNA and protein expression and observed a significant increase in the m6A methylation status of total RNA in the GC cells and tissues. METTL3 knockdown inhibited total RNA m6A methylation level, as well as cell proliferation and migration capacity. Moreover, METTL3 knockdown decreased α-smooth muscle actin. Taken together, our finding revealed that m6A methylation writer METTL3 serve as an oncogene in tumorigenesis of GC.

Prognostic value of a two-microRNA signature for papillary thyroid cancer and a bioinformatic analysis of their possible functions.

BACKGROUND: Recent scientific evidence has suggested that microRNAs (miRNAs) play an important role in papillary thyroid cancer (PTC). In the current study, we aim to identify a miRNA-related signature as the sensitive and novel prognostic biomarkers. METHODS: We performed a comprehensive analysis of the data downloaded from the Cancer Genome Atlas (TCGA) database. The association between survival outcome and miRNA was assessed by the univariate and multivariate Cox proportional hazards model. The risk score model was built to evaluate the predicting value of miRNA signature. The potential biofunctions and transcription factors of target miRNAs were investigated through bioinformatic analysis. The result was verified by the quantitative real-time polymerase chain reaction (qRT-PCR) in 32 pairs of PTC and adjacent nontumor tissues. In addition, the results were verified by other cohorts from gene expression omnibus (GEO) as detected by microarrays. RESULTS: A total of 1030 miRNAs were identified from the TCGA database. Thirty-six key intersection miRNAs were obtained. The associations between clinical features and key miRNAs were evaluated. Eventually, a two-miRNA signature (hsa-miR-181a-2-3p and hsa-miR-138-1-3p) was identified. The power of the miRNA prognostic signature was effective. In total, we identified 202 genes that were associated with 2 miRNAs above, and the top 10 enriched transcript factors that highly related with the target miRNAs were explored. The qRT-PCR and GEO data validation were consistent with bioinformatics results. CONCLUSIONS: A tumor-specific miRNA signature was identified, and the joint prognostic power was evaluated, which may be potential biomarkers for prognosis of PTC. IMPACT: The two-miRNA signature could become the potential prognostic indicator of PTC in the future.

miR-93-5p Transferred by Exosomes Promotes the Proliferation of Esophageal Cancer Cells via Intercellular Communication by Targeting PTEN.

OBJECTIVE: To investigate the relationship between plasma miR-93-5p and the risk of esophageal cancer, as well as the influence of miR-93-5p on the biological function of esophageal cancer cells, exerted through exosomes. METHODS: The expression of plasma miR-93-5p in esophageal cancer patients and healthy controls was analysed by real-time quantitative PCR. The influence of miR-93-5p on the risk and prognosis of esophageal carcinoma was analyzed by conditional logistic regression and survival analysis. The effect of miR-93-5p on the biological function of recipient cells was investigated by establishing an in vitro donor cell co-culture model. The target gene of miR-93-5p was validated by luciferase reporter assay and Western Blotting. RESULTS: Upregulation of plasma miR-93-5p expression significantly increases the risk of esophageal cancer and is associated with poor prognosis. miR-93-5p transferred by exosomes promotes the proliferation of recipient esophageal cancer cells and affects the expression of PTEN and its downstream proteins p21 and cyclin D1. CONCLUSION: Our study provides a reference for the identification of biomarkers for the diagnosis and prognosis of esophageal cancer.

Differential immunosuppression by Campoletis chlorideae eggs and ichnovirus in larvae of Helicoverpa armigera and Spodoptera exigua.

The ichneumonid wasp, Campoletis chlorideae Uchida, successfully develops in the cotton bollworm Helicoverpa armigera (Hübner), but rarely survives in the beet armyworm Spodoptera exigua (Hübner) due to the encapsulation by host immunity. In this study, we investigated the role of C. chlorideae ichnovirus (CcIV) and eggs in the evasion of the host immune system. Washed eggs of different types, immature, mature, newly laid, or pretreated with protease K, were injected alone or with the calyx fluid containing CcIV into the larvae of H. armigera and S. exigua. In H. armigera, when injected with washed eggs alone, only 9.5% of the mature eggs were encapsulated at 24h post-injection. This is much lower than that of the immature eggs (100%), mature eggs pretreated with protease K (100%) and newly laid eggs (54.4%). No encapsulation was observed when the washed eggs were co-injected with calyx fluid at 24h post-injection. Conversely, the eggs in all treatments were encapsulated in S. exigua. Electron microscopic observations of parasitoid eggs showed structural differences between the surfaces of the mature and other kinds of eggs. The injected CcIV decreased the numbers of host hemocytes and suppressed the spreading ability of plasmatocytes and granulocytes in H. armigera, but had little effect on the hemocytes from S. exigua. In conclusion, the C. chlorideae egg provides a passive protection against encapsulation by itself, and CcIV supplies an active protection through disrupting host immune responses. These coordinated protections are host-specific, implying their role in host range determination.

Isolation and characterization of an algicidal bacterium indigenous to lake Taihu with a red pigment able to lyse microcystis aeruginosa.

OBJECTIVE: To isolate and characterize indigenous algicidal bacteria and their algae-lysing compounds active against Microcystis aeruginosa, strains TH1, TH2, and FACHB 905. METHODS: The bacteria were identified using the Biolog automated microbial identification system and 16S rDNA sequence analysis. The algae-lysing compounds were isolated and purified by silica gel column chromatography and reverse-phase high performance liquid chromatography. Their structures were confirmed by Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared (FT-IR) spectroscopy. Algae-lysing activity was observed using microscopy. RESULTS: The algae-lysing bacterium LTH-2 isolated from Lake Taihu was identified as Serratia marcescens. Strain LTH-2 secreted a red pigment identified as prodigiosin (C20H25N3O), which showed strong lytic activity with algal strains M. aeruginosa TH1, TH2, and FACHB 905 in a concentration-dependent manner. The 50% inhibitory concentration (IC50) of prodigiosin with the algal strains was 4.8 (± 0.4)× 10⁻² µg/mL, 8.9 (± 1.1)× 10⁻² µg/mL, and 1.7 (± 0.1)× 10⁻¹ µg/mL in 24 h, respectively. CONCLUSION: The bacterium LTH-2 and its pigment had strong Microcystis-lysing activity probably related to damage of cell membranes. The bacterium LTH-2 and its red pigment are potentially useful for regulating blooms of harmful M. aeruginosa.

Chlorpyrifos exposure reduces reproductive capacity owing to a damaging effect on gametogenesis in the nematode Caenorhabditis elegans.

Previous studies have revealed that chlorpyrifos exposure adversely affects the reproductive capacity of male rodents. The present study investigated the reproductive toxicity of chlorpyrifos exposure and possible related mechanisms using the nematode Caenorhabditis elegans. L4 nematode larvae were exposed to chlorpyrifos at concentrations of 0.003, 0.03, 0.3 and 3.0 mg l(-1) for different durations. In addition to decreased brood size, reduced spermatid size, increased percentage of abnormal spermatids, suppressed spermatid activation and motility of sperm, damaged oocyte morphology, increased numbers of apoptotic cells and unfertilized oocytes were observed in nematodes exposed to various concentrations of chlorpyrifos. Moreover, expression patterns of the genes spe-10, spe-15, fer-1, prg-1, glp-1, mlh-1, cyb-3, ced-3, ced-4 and ced-9 (which are associated with spermatid size, spermatid activation and morphology, oocyte morphology, oocyte function, and apoptosis) were altered after chlorpyrifos exposure. Therefore, chlorpyrifos exposure may adversely affect fertility in nematodes by influencing both spermatogenesis and oogenesis. Alterations in the expression patterns of genes involved in gametogenesis may explain the corresponding changes in gametogenesis in nematodes exposed to chlorpyrifos. Hence, the model organism Caenorhabditis elegans is recommended for assessment of reproductive toxicity relating to gametogenesis.

ZnO, TiO(2), SiO(2,) and Al(2)O(3) nanoparticles-induced toxic effects on human fetal lung fibroblasts.

OBJECTIVE: This study aims to investigate and compare the toxic effects of four types of metal oxide (ZnO, TiO(2), SiO(2,) and Al(2)O(3)) nanoparticles with similar primary size (∼20 nm) on human fetal lung fibroblasts (HFL1) in vitro. METHODS: The HFL1 cells were exposed to the nanoparticles, and toxic effects were analyzed by using MTT assay, cellular morphology observation and Hoechst 33 258 staining. RESULTS: The results show that the four types of metal oxide nanoparticles lead to cellular mitochondrial dysfunction, morphological modifications and apoptosis at the concentration range of 0.25-1.50 mg/mL and the toxic effects are obviously displayed in dose-dependent manner. ZnO is the most toxic nanomaterials followed by TiO(2), SiO(2), and Al(2)O(3) nanoparticles in a descending order. CONCLUSION: The results highlight the differential cytotoxicity associated with exposure to ZnO, TiO(2), SiO(2), and Al(2)O(3) nanoparticles, and suggest an extreme attention to safety utilization of these nanomaterials.

The immune toxicity of titanium dioxide on primary pulmonary alveolar macrophages relies on their surface area and crystal structure.

Surface properties are critical to assess effects of titanium dioxide (TiO2) primary nanoparticles on the immune function of pulmonary alveolar macrophage (PAMs). In this study the immune toxicity of TiO2 primary nanoparticles on PAMs relies on their surface area and crystal structure were determined. The primary PAMs of rats exposed to different sizes and crystal structure of TiO2 particles at different dosages for 24 hrs were evaluated for cytokines, phagocytosis, chemotaxis and surface molecules expression. Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) level of PAMs significantly increased when exposed to TiO2 primary particles and there were significant association with the exposure total surface area and crystal structure of TiO2 particles in the former. TiO2 particles showed significant inhibiting effects on phagocytotic ability, chemotactic ability, Fc receptors and MHC-II molecular expression of macrophages compared with control. Exposure dosage and crystal structure of TiO2 particles play effects on phagocytotic ability and chemotactic ability of PAMs. These results suggested that TiO2 nanoparticles could induce the release of inflammatory mediators, initiate the inflammation development and inhibit the immune function of PAMs associated with non-specific immunity and specific immunity relies on surface area and crystal structure. NO activity might be a candidate marker indicating the TiO2 exposure burden and cell damage in PAMs.

The N6-Methyladenosine (m6A) Methylation Gene YTHDF1 Reveals a Potential Diagnostic Role for Gastric Cancer.

PURPOSE: Gastric cancer (GC) is aggressive cancer with a high mortality rate worldwide. N6-methyladenosine (m6A) RNA methylation is related to tumorigenesis, which is dynamically regulated by m6A modulators ("writer," "eraser," and "reader"). We conducted a comprehensive analysis of the m6A genes of GC patients in TCGA datasets to identify the potential diagnostic biomarkers. MATERIALS AND METHODS: We analyzed the expression profile of m6A genes in the TCGA cohort and constructed a diagnostic-m6A-score (DMS) by the LASSO-logistic model. In addition, by consensus cluster analysis, we identified two different subgroups of GC risk individuals by the expression profile of m6A modulators, revealing that YTHDF1's expression variation profile in GC diagnosis. We also performed RT-qPCR and WB verification in 17 pairs of GC specimens and paired adjacent non-tumor tissues and GC cell lines, and verified the expression trend of YTHDF1 in five GEO GC datasets. YTHDF1 expression and clinical features of GC patients were assessed by the UALCAN. RESULTS: The DMS with high specificity and sensitivity (AUC = 0.986) is proven to distinguish cancer from normal controls better. Moreover, we found that the expression profile variation of YTHDF1 was significantly associated with the high-risk subtype of GC patients. RT-qPCR and Western blot results are consistent with silicon analysis, revealing that YTHDF1's potential oncogene role in GC tumor. CONCLUSION: In conclusion, we developed the m6A gene-based diagnostic signature for GC and found that YTHDF1 was significantly correlated with the high-risk subtype of GC patients, suggesting that YTHDF1 might be a potential target in GC early diagnosis.

Evaluation of pesticide toxicities with differing mechanisms using Caenorhabditis elegans.

The aim of this study was to (1) determine whether model organism Caenorhabditis elegans was sensitive to pesticides at the maximum concentration limits regulated by national agency standards, and (2) examine the multi-biological toxicities occurring as a result of exposure to pesticides. Five pesticides, namely, chlorpyrifos, imibacloprid, buprofezin, cyhalothrin, and glyphosate, with four different mechanisms of action were selected for the investigation. In accordance with national agency requirements, 4 exposed groups were used for each tested pesticide with the concentration scales ranging from 1.0 x 10(-3) to 1 mg/L. L4 larvae were exposed for 24 and 72 h, respectively. Endpoints of locomotion, propagation, and development were selected for the assay as parameters of toxicity. After exposure for 24 h, both the body bend frequency and head thrash frequency of nematodes exposed to chlorpyrifos, imibacloprid, and cyhalothrin decreased in a concentration-dependent manner, and there were significant differences between exposed groups at maximum concentration level (MCL) compared to control. The generation time of nematodes exposed to buprofezin 24 h significantly increased in a concentration-dependent manner in the highest exposed group. When exposed for 72 h, the body bend frequency and head thrash frequency of nematodes exposed to cyhalothrin markedly decreased at MCL. The generation time and brood size of nematodes exposed to buprofezin were reduced in a concentration-dependent manner. The behavior of nematodes was sensitive to pesticides with neurotoxic properties, while pesticides affecting insect growth modified the reproductive system. The effects of pesticides on nematodes exposed for 24 h appeared more sensitive than with exposure for 72 h. Caenorhabditis elegans may thus be used for assessing the adverse effects of pesticide residues in aquatic environment.

Integrated analysis of long non­coding RNA competing interactions revealed potential biomarkers in cervical cancer: Based on a public database.

Cervical cancer (CC) is a common gynecological malignancy in women worldwide. Using an RNA sequencing profile from The Cancer Genome Atlas (TCGA) and the CC patient information, the aim of the present study was to identify potential long non­coding RNA (lncRNA) biomarkers of CC using bioinformatics analysis and building a competing endogenous RNA (ceRNA) co­expression network. Results indicated several CC­specific lncRNAs, which were associated with CC clinical information and selected some of them for validation and evaluated their diagnostic values. Bioinformatics analysis identified 51 CC­specific lncRNAs (fold­change >2 and P<0.05), and 42 of these were included in ceRNA network consisting of lncRNA­miRNA­mRNA interactions. Further analyses revealed that differential expression levels of 19 lncRNAs were significantly associated with different clinical features (P<0.05). A total of 11 key lncRNAs in the ceRNA network for reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis to detect their expression levels in 31 pairs of CC clinical samples. The results indicated that 7 lncRNAs were upregulated and 4 lncRNAs were downregulated in CC patients. The fold­changes between the RT­qPCR experiments and the TCGA bioinformatics analyses were the same. Furthermore, the area under the receiver operating characteristic (ROC) curve of four lncRNAs (EMX20S, MEG3, SYS1­DBNDD2 and MIR9­3HG) indicated that their combined use may have a significant diagnostic value in CC (P<0.05). To the best of our knowledge, the present study is the first to have identified CC­specific lncRNAs to construct a ceRNA network and has also provided new insights for further investigation of a lncRNA­associated ceRNA network in CC. In additon, the verification results suggested that the method of bioinformatics analysis and screening of lncRNAs was accurate and reliable. To conclude, the use of multiple lncRNAs may thus improve diagnostic efficacy in CC. In addition, these specific lncRNAs may serve as new candidate biomarkers for clinical diagnosis, classification and prognosis of CC.

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.

Identification and functional characterization of long non-coding RNAs in human gastric cancer.

Abnormal regulation of long non-coding RNAs (lncRNAs) appears to be a primary feature of numerous types of human cancer. However, the association between the dysregulation of lncRNAs and functional alterations in gastric cancer (GC) remains unclear. In previous studies, we applied microarray and bioinformatics analyses to screen for key lncRNAs from the tumor tissues and matched adjacent non-tumor tissues of 10 patients with GC. There were seven key lncRNAs demonstrated to be significantly different between carcinoma tissues and adjacent non-tumor tissues. In the present study, the expression of these seven selected lncRNAs were validated in 82 patients with GC to further investigate the association between lncRNAs and GC clinical characterization. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results demonstrated that RP5-919F19, MCPH1 antisense RNA 1 (CTD-2541M15) and urothelial carcinoma-associated 1 (UCA1) exhibited consistent upregulation in cancer compared with adjacent non-tumor tissues, whereas AP000459, LOC101928316, tumor suppressor candidate 8 (LINC01071) and maternally expressed 3 (MEG3) showed consistent downregulation. The results from the microarray and RT-qPCR experiments achieved 100% agreement. A correlation analysis indicated that RP5-919F19, LOC101928316 and MEG3 were significantly associated with tumor differentiation degree, RP5-919F19, UCA1 and MEG3 were significantly associated with lymph node metastasis, and RP5-919F19, CTD-2541M15 and UCA1 were significantly associated with tumor-node-metastasis stage (P<0.05). In addition, it was identified that the differential expression of LINC01071 and LOC101928316 significantly correlated with the age and gender of the GC patients, respectively (P<0.05). The results suggest that the lncRNAs RP5-919F19, LOC101928316, CTD-2541M15, UCA1 and MEG3 are closely associated with the invasion and metastasis of GC, which reveals these indicators as potential specificity biomarkers for the diagnosis, prognosis and classification of GC. Thus, these lncRNAs merit further study as novel candidate biomarkers for the clinical diagnosis of GC and as potential targets for therapy.

Reduced expression of human DNA repair genes in esophageal squamous-cell carcinoma in china.

Epidemiological studies indicated that the incidence of esophageal squamous-cell carcinoma (ESCC) is associated with exposure to a variety of environmental factors. To determine whether the baseline expression of genes involved in DNA damage and repair induced by these carcinogens is associated with higher risk for ESCC, a case-control study was undertaken and the relative expression levels of six DNA repair genes (MGMT, hOGG1, XRCC1, XPD, hMLH1, and hMSH2) were determined in peripheral blood mononuclear cells (PBMC). One hundred patients with newly diagnosed, untreated ESCC and 117 healthy controls matched for age, gender, and residence were recruited. Expression levels of six genes were measured by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR). Compared with controls, the relative expression levels of hMLH1, hMSH2, XRCC1, XPD, and MGMT, were significantly altered in ESCC patients. Using the median of relative expression level in controls as the cutoff point, results also demonstrated an increased risk for ESCC associated with reduced expression of hMSH2, XRCC, XPD, and MGMT. The expression levels of four genes (hMSH2, XRCC1, XPD, MGMT) present in PBMC were significantly correlated with increased risk for ESCC, in which there was reduced expression of MGMT, suggesting an important etiology role for MGMT expression in the initiation of ESCC in Huaian of China.

Analysis of multiple single nucleotide polymorphisms (SNPs) of myeloperoxidase (MPO) to screen for genetic markers associated with acute leukemia in Chinese Han population.

Myeloperoxidase (MPO) is an important metabolizing enzyme involved in oxidative stress responses to some environmental carcinogens including benzene, a chemical associated with bone marrow toxicity and leukemia. A novel multiplex polymerase chain reaction (PCR) technique based on adapter-ligation mediated allele-specific amplification (ALM-ASA) is simple, inexpensive and especially useful for multiplex single nucleotide polymorphisms (SNPs) genotyping. The purpose of this study was to examine the genetic markers associated with acute leukemia from multiple SNPs of MPO found in Chinese Han population. A case-control study was conducted, with 135 patients with adult acute leukemia and 187 cancer-free subjects as a control group. Nine SNPs in promoter and exons were selected that were markers related to gene function and risk of leukemia development. The multiplex PCR technique based on ALM-ASA was used to detect multiple SNP genotypes. The accuracy of ALM-ASA was tested by sequence and PCRrestriction fragment length polymorphism (RFLP) genotyping analysis. No polymorphisms were found at -1468T > C, -1053T > C, 958C > T, 967C > A, 1033 T > C. A marked linkage disequilibrium was found among -1816, -586, and -463 genotypes. Three haplotypes were constructed. SNP and haplotypes analysis showed the frequency of the MPO -463G > A mutant genotypes (G/A+A/A) was significantly less in cancer cases. The results of sequence and PCR-RFLP yielded results similar to ALM-ASA. Data suggest that MPO G-463A mutant genotypes may be associated with a reduced risk of acute leukemia development due to diminished activation of carcinogens. MPO G-463A variant may possess a protective genetic marker against acute leukemia in the Chinese Han population.

Association of combined CYP2E1 gene polymorphism with the risk for esophageal squamous cell carcinoma in Huai'an population, China.

BACKGROUND: Cytochrome P450 2E1 (CYP2E1) has an important role in the metabolic activation of precarcinogens such as N-nitrosoamines and other low relative molecular mass, organic compounds. This study examined whether CYP2E1 RsaI and DraI polymorphism are associated with susceptibility to esophageal squamous cell carcinoma and the correlation between the genotypes and expression levels of CYP2E1 mRNA. METHODS: Seventy-seven patients with newly diagnosed, untreated esophageal squamous cell carcinoma and 79 healthy controls matched in age, gender and residence were recruited for the control study. An RsaI polymorphism in the 5'-flanking region and a DraI polymorphism in the sixth intron of the CYP2E1 gene, which could possibly affect its transcription, were determined in this study by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and mRNA level of CYP2E1 was measured by quantitative real-time reverse transcription PCR. RESULTS: No significant association of RsaI or DraI polymorphism of CYP2E1 with susceptibility of esophageal squamous cell carcinoma were demonstrated (OR = 1.67, 95% CI: 0.89 - 3.15, P = 0.11; OR = 1.11, 95% CI: 0.59 - 2.09, P = 0.74, respectively). With SHEsis software, no linkage disequilibrium was detected between RsaI and DraI polymorphism (D' = 0.528, r(2) = 0.27). When combined RsaI polymorphism with DraI polymorphism, the association between that carrying c2 allele and DD genotype and the risk for esophageal squamous cell carcinoma were found (OR = 5.77, 95% CI: 1.65 - 20.22). Compared with the normal controls, the mRNA levels with RsaI polymorphism, DraI polymorphism, or any combined genotypes in cases showed no statistical difference. CONCLUSIONS: This study suggests that carrying c2 allele and DD genotype conferreded an elevated risk for esophageal squamous cell carcinoma. There was no significant statistical relationship between the genotypes c1/c2, D/C, or the combined allele and mRNA expression.

Comprehensive analysis of a novel four-lncRNA signature as a prognostic biomarker for human gastric cancer.

Emerging evidence indicates that long non-coding RNAs (lncRNAs) play a crucial role in predicting survival for gastric cancer (GC) patients. This study aims to identify a lncRNA-related signature for evaluating the overall survival of 379 GC patients from The Cancer Genome Atlas (TCGA) database. The associations between survival outcome and the expression of lncRNAs were evaluated by the univariate and multivariate Cox proportional hazards regression analyses. Four lncRNAs (LINC01018, LOC553137, MIR4435-2HG, and TTTY14) were identified as significantly correlated with overall survival. These four lncRNAs were gathered as a single prognostic signature. There was a significant positive correlation between GC patients with low-risk scores and overall survival (P = 0.001). Further analysis suggested that the prognostic value of this four-lncRNA signature was independent in clinical features. Gene set enrichment analysis found that these four lncRNAs were correlated with several molecular pathways of the tumor. Our study indicates that this novel lncRNA expression signature may be a useful biomarker of the prognosis for GC patients, based on bioinformatics analysis.

Trends of long noncoding RNA research from 2007 to 2016: a bibliometric analysis.

PURPOSE: This study aims to analyze the scientific output of long noncoding RNA (lncRNA) research and construct a model to evaluate publications from the past decade qualitatively and quantitatively. METHODS: Publications from 2007 to 2016 were retrieved from the Web of Science Core Collection database. Microsoft Excel 2016 and CiteSpace IV software were used to analyze publication outputs, journals, countries, institutions, authors, citation counts, ESI top papers, H-index, and research frontiers. RESULTS: A total of 3,008 papers on lncRNA research were identified published by June 17, 2017. The journal, Oncotarget (IF2016, 5.168) ranked first in the number of publications. China had the largest number of publications (1,843), but the United States showed its dominant position in both citation frequency (45,120) and H-index (97). Zhang Y (72 publications) published the most papers, and Guttman M (1,556 citations) had the greatest co-citation counts. The keyword "database" ranked first in research frontiers. CONCLUSION: The annual number of publications rapidly increased in the past decade. China showed its significant progress in lncRNA research, but the United States was the actual leading country in this field. Many Chinese institutions engaged in lncRNA research but significant collaborations among them were not noted. Guttman M, Mercer TR, Rinn JL, and Gupta RA were identified as good candidates for research collaboration. "Database," "Xist RNA," and "Genome-wide association study" should be closely observed in this field.