Identification by TCGA database search of five genes that are aberrantly expressed and involved in hepatocellular carcinoma potentially via DNA methylation changes

BACKGROUND@#Various treatments for hepatocellular carcinoma (HCC) are utilized in clinical practice; however, the prognosis is still poor on account of high recurrence rates. DNA methylation levels of CpG islands around promoters (promoter CpGis) inversely regulate gene expression and closely involved in carcinogenesis. As a new strategy, several chemicals globally inhibiting DNA methylation have been developed aiming at reducing DNA methylation levels and maintaining the expression of tumor suppressor genes. On the other hand, since these drugs nonspecifically modify DNA methylation, they can cause serious adverse effects. In order to ameliorate the methods by targeting specific CpGs, information of cancer-related genes that are regulated by DNA methylation is required.@*METHODS@#We searched candidate genes whose expressions were regulated by DNA methylation of promoter CpGi and which are involved in HCC cases. To do so, we first identified genes whose expression were changed in HCC by comparing gene expressions of 371 HCC tissues and 41 non-tumor tissues using the Cancer Genome Atlas (TCGA) database. The genes were further selected for poor prognosis by log-rank test of Kaplan-Meier plot and for cancer relevance by Pubmed search. Expression profiles of upregulated genes in HCC tissues were assessed by Gene Ontology (GO) analysis. Finally, using DNA methylation data of TCGA database, we selected genes whose promoter DNA methylation levels were inversely correlated with gene expression.@*RESULTS@#We found 115 genes which were significantly up- or downregulated in HCC tissues and were associated with poor prognosis and cancer relevance. The upregulated genes were significantly enriched in cell division, cell cycle, and cell proliferation. Among the upregulated genes in HCC, we identified hypomethylation of CpGis around promoters of FANCB, KIF15, KIF4A, ERCC6L, and UBE2C. In addition, TCGA data showed that the tumor suppressor gene P16 is unexpectedly overexpressed in many types of cancers.@*CONCLUSIONS@#We identified five candidate genes whose expressions were regulated by DNA methylation of promoter CpGi and associate with cancer cases and poor prognosis in HCC. Modification of site-specific DNA methylation of these genes enables a different approach for HCC treatment with higher selectivity and lower adverse effects.

Effects of 1-bromopropane on neurological and hematological changes of female exposed workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the health effects of 1-bromopropane (1-BP) on female exposed workers.</p><p><b>METHODS</b>Four 1-BP manufacturing plants were investigated. Workers were interviewed with questionnaire and examined with neurobehavioral core test battery, nerve conduction velocity tests of nervus tibialis and nervus suralis, vibration sensation test, hematological and biochemical tests. Ambient 1-BP concentration was measured with detection tube, and time-weighed average levels of individual workers were estimated with passive samplers.</p><p><b>RESULTS</b>1-BP concentration in the plants ranged from 0 to 402.40 mg/m3 (Geomean 32.19 mg/m3). Time-weighted average exposure levels (TWA-8 h) ranged from 0.35 to 535.19 mg/m3 (Geomean 14.08 mg/m3). Compared with the control group, 1-BP exposed workers showed reduced motor nerve conduction velocity [(44.8 +/- 8.7) m/s] and sensory nerve conduction velocity [(45.5 +/- 4.9) m/s], prolonged distal latency [(7.5 +/- 2.1) ms], reduced toe vibration perception, and altered neurobehavior parameters(POMS vigor, tension, anxiety, confusion) significantly (P < 0.05). As to hematological and biochemical indicators, the exposed workers showed decreased white blood cell count [(5.6 +/- 2.17) x 10(3)/microl], red blood cell count [(3.9 +/- 0.4) x 10(6)/microl], hemoglobin [(121.1 +/- 14.5) g/L] and creatine kinase [(82.0 +/- 27.5) IU/L] (P < 0.05), and increased serum total protein (8.0 +/- 0.5 g/dl), lactate dehydrogenase [(335.2 +/- 356.6) IU/L], thyroid-stimulating hormone [(3.6 +/- 2.3) microIU/ml] and follicle-stimulating hormone levels (18.7 +/- 24.4 mIU/ml) (P < 0.05).</p><p><b>CONCLUSION</b>1-BP exposure may affect peripheral nerves and central nervous system, and lead to abnormal hematological and biomedical indicators.</p>

Exposure to 1-bromopropane causes dose-dependent neurological abnormalities in workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the dose-effect relationship between 1-bromopropane (1-BP) exposure and health effects in workers.</p><p><b>METHODS</b>Occupational field investigations were conducted in 1-BP factories. Ambient 1-BP concentrations were detected with detection tube, and the 8 h time-weighted average individual exposure levels (TWA-8 h) were measured by passive sampler. Workers underwent questionnaire survey, neurological examination, nerve conduction velocity examination, vibration sensation test. routine blood test as well as blood biochemical test. According to TWA values or TWA x duration values, workers were divided into three dose groups for dose-effect relationship analysis. USEPA BMDS 2.1 software was applied to calculate 1-BP benchmark dose (BMD) and its 95% lower limit (BMDL).</p><p><b>RESULTS</b>The TWA-8h concentrations ranged from 0.35 to 535.19 mg/m3 (geo-mean 14.08 mg/m3). Dose-dependent analysis showed that the motor nerve distal latency (linear regression coefficient was 0.066 6), vibration sensation of toes (linear regression coefficient were 0.157 2 and 0.193 9), creatine kinase (linear regression coefficient was -1.05) and thyroid stimulating hormone levels (linear regression coefficient was 0.1024) of 1-BP exposed workers changed in a dose-dependent manner (P < 0.05). BMD calculation based on DL as 1-BP toxic effect endpoint showed that TWA-8h of the BMD values and BMDL values were 50.55 mg/m3 and 30.78 mg/m3, respectively.</p><p><b>CONCLUSION</b>1-BP causes dose-dependent changes in tibial nerve DL, vibration sensation, CK and TSH levels.</p>