Abstract Background 7-dehydrocholesterol reductase (DHCR7) is a key enzyme involving the final step of cholesterol synthesis pathway. Abnormalities in the DHCR7 gene can lead to a variety of diseases, such as Smith-Lemli-Opitz syndrome. However, the relationship between DHCR7 and oncogenesis remain unclear. Methods We used several bioinformatic databases which the original data from the TCGA and GEO database. Briefly, the gene of DHCR7 expression were explored by the Oncomine, TIMER and GEPIA databases. The effect of DHCR7 on prognosis was analyzed via Kaplan-Meier plotter and GEPIA database. The TISIDB database was used to determine the relationship between DHCR7 expression and pan-cancer stages and the DHCR7 expression in different immune and molecular subtypes of human cancers. The correlations between DHCR7 expression and immune checkpoints (ICP), tumor mutational burden (TMB), microsatellite instability (MSI), mutant-allele tumor heterogeneity (MATH), neoantigens and infiltrating immune cells of human cancers and urogenital cancers were analyzed through the SangerBox database (http://vip.sangerbox.com/login.html). The genomic alterations of DHCR7 were analyzed by the c-BioPortal database. The differential expression of DHCR7 in urogenital cancers with different clinical characteristics was analyzed with the UALCAN database. The DHCR7 co-expression genes in BLCA was analyzed through the Linked Omics database. And the association between DHCR7 and related genes and markers of immune cells were analyzed by TIMER database. Results The results indicated that DHCR7 was highly expressed in most cancers, except in Cholangio carcinoma, Pheochromocytoma and Paraganglioma. Aberrantly expressed DHCR7 was associated with the poor prognosis, advanced tumor stage and metastasis in most tumor types. Additionally, significant strong correlations between DHCR7 expression and tumor immune-infiltrated cells (TILs), ICP, TMB, MSI, MATH and neoantigens showed in most human cancers, and marker genes of TILs were significantly related to DHCR7 expression in BLCA, KIRC and PRAD. DHCR7 co-expression networks mostly participated in the regulation of immune response regulating signaling pathway, leukocyte differentiation and angiogenesis. Conclusion Through pan-cancer analysis, DHCR7 may serve as a potential prognostic and immunological pan-cancer biomarker, especially in urological tumors.
This study aims to observe the changes of myocardial injuries after the firearm wound-induced intestinal perforation in porcine abdomen. 42 healthy Landrace piglets were randomly divided into the control group and the injury group, which was then subdivided into the post-injury 1 h, 2 h, 4 h, 8 h, 12 h and 24 h subgroup. the LDH, CK and CK-MB levels of each group, as well as the plasma endotoxin, were determined and compared. The plasma endotoxin levels of the experimental groups were significantly higher than the control group, and the light microscope observation revealed that the 8 h, 12 h and 24 h subgroup appeared the gradually-aggravated myocardial cell edema and degeneration; the electron microscope revealed that the 4 h, 8 h, 12 h and 24 h subgroup appeared the mitochondrial swelling and dissolution gradually; the serum levels of LDH, CK and CK-MB of each experimental group were higher than the control group. The abdominal firearm wound-induced intestinal perforation would lead to the damaged changes of myocardial morphology and enzymes, which would aggravate as time went along.
Objective To explore the correlation between X/preC region mutations in HBV genotype C and HCC.Methods Serum samples from patients with HCC and chronic HBV infection (non-HCC) were collected in Wenzhou Chinese Medicine Hospital from September 2010 to June 2013.HBV genotypes were determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP),and then the samples of genotype C HBV were sequenced for the mutations in X/preC region.Results The single base mutation frequencies in X/preC region in HCC patients were G1764A (97.67％),A1762T (95.35％),G1896A (80.23％),T1753V (59.30％),A1846T(55.81％),C1653T(44.18％),G1613A(40.67％) and G1899A(32.59％) in order,which were all higher than those in non-HCC patients with significant differences (x2=23.604,22.956,14.902,34.318,26.078,10.623,6.137 and 13.464,P all＜0.05).Moreover,the proportion of HCC patients with multi-mutation (the total number of mutations ≥4 in X/preC region) was 88.37％(76/86),which was higher than that of non-HCC patients [31.48％(34/108)],with a significant difference(x2=63.122,P＜0.01).Conclusions HBV related HCC patients have higher gene mutation frequency and multiple mutational sites in X/preC region than non-HCC patients do.
Key words:
Hepatitis B virus; Hepatocellular carcinoma; X/preC region; Gene mutation
Aberrant microRNA expression is common in colorectal cancer and DNA methylation is believed to be responsible for this alteration. In this study, we performed evaluation in vivo and in vitro to determine the role of miR-181b as a potential diagnostic and prognostic biomarker in colorectal cancer. Ninety-seven pairs of colorectal cancer tissues and adjacent normal tissues were collected. The expression level and methylation status of miR-181b was determined in tissue samples and multiple colorectal cancer cell lines. RASSF1A, a predicted target gene of miR-181b, was investigated in vitro. Further mechanistic explorations were conducted. It was found that miR-181b expression was frequently downregulated in cancer samples. This lower expression level resulted from higher hypermethylation in cancer tissue and was closely related to TNM stage. Following artificial synthesis of miR-181b stimulation, colorectal cancer cell proliferation was greatly inhibited in CRC cells while apoptosis percentage markedly increased. miR-181b achieved the tumor suppressive effects via direct targeting of the RASSF1A gene. This study indicated the clinical significance of miR-181b and the influence of miR-181b promoter region in epigenetic silencing of tumorigenicity in colorectal cancer, and implied the possible usage of miR-181b as a diagnostic and prognostic biomarker in colorectal cancer.
Objective The prognostic value of neutrophil-to-lymphocyte ratio (NLR) combined with Model for End-Stage Liver Disease (MELD) score was evaluated for hepatitis B virus-associated decompensated cirrhosis (HBV-DeCi).
Abstract Tumor-derived exosomes are important for cell-cell communication. However, the role of TP53 in the control of exosome production in colorectal cancer (CRC) is controversial and unclear. The features of exosomes secreted from HCT116 TP53 -wild type (WT), TP53 -knockout (KO) and constructed TP53 (R273H)-mutant (MT) cells were assessed. The exosomes from the MT and KO cells exhibited significantly reduced sizes compared with the WT cells. A comprehensive proteomic analysis of exosomal proteins was performed using the isobaric tag for relative and absolute quantitation (iTRAQ)-2D-LC-MS/MS strategy. A total of 3437 protein groups with ≥2 matched peptides were identified. Specifically, hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) was consistently down-regulated in the exosomes from the MT and KO cells. Functional studies demonstrated that low HGS levels were responsible for the decreased exosome size. TP53 regulated HGS expression and thus HGS-dependent exosome formation. Furthermore, the HGS expression was gradually increased concomitant with CRC carcinogenesis and was an independent poor prognostic factor. In conclusion, a novel HGS-dependent TP53 mechanism in exosome formation was identified in CRC. HGS may serve as a novel prognostic biomarker and a candidate target for therapeutic interventions.
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