ABSTRACT
Hepatocellular carcinoma (HCC) is a complex polygenic disease whose development is dependent on many genetic factors. The let-7 family, an important and widely studied microRNA family, has been shown to play an important role in the initiation and progression of HCC. In this study, we examined the possible associations between single-nucleotide polymorphisms in the promoter region of the let-7 family (rs10877887) and the susceptibility and prognosis of HCC, using a case-control research model. Eighty-nine HCC patients and 95 healthy controls were genotypes by direct sequencing, and the correlation between rs10877887 genotypes and HCC susceptibility was evaluated using an unconditional logistic regression model. Populations with the CT + CC genotype were at a significantly higher risk of HCC compared to those with the TT genotype (CT + CC vs TT: odds ratio = 3.52, 95% confidence interval = 1.90-6.52; P < 0.05). Furthermore, we discovered that the genetic variant of rs10877887 might serve as a prognostic marker for survival in HCC patients, as the CT + CC genotype was associated with poor prognosis.
Subject(s)
Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , MicroRNAs/genetics , Aged , Asian People/genetics , Carcinoma, Hepatocellular/metabolism , Case-Control Studies , China , Female , Genetic Predisposition to Disease , Genetic Variation , Humans , Liver Neoplasms/metabolism , Male , MicroRNAs/metabolism , Middle Aged , Polymorphism, Single Nucleotide , Prognosis , Promoter Regions, GeneticABSTRACT
The aim of this meta-analysis was to investigate the overall diagnostic and prognostic values of CTHRC1 expression in human cancer development. Based on the inclusion and exclusion criteria, 8 cohort studies were included in the meta-analysis. The data were extracted, and analyses were performed using a random-effects model. Summary odds ratios (ORs) and effect sizes (ESs) with 95% confidence intervals (CIs) were calculated to assess the strength of the associations. A total of 1065 cancer patients from the 8 studies were included in the meta-analysis. The results revealed a positive correlation of CTHRC1 protein expression in tumors with tumor-node-metastasis (TNM) stage and with lymph node (LN) metastasis (TNM: OR = 2.98, 95%CI = 1.48-6.00, P = 0.002; LN: OR = 4.26, 95%CI = 1.88-9.67, P = 0.001). CTHRC1 expression was higher in tumors with sizes ≥5 cm than in tumors with sizes <5 cm (OR = 2.39, 95%CI = 1.12-5.09, P = 0.024). Patients with higher CTHRC1 expression had decreased overall survival (OS) (ES = 1.78, 95%CI = 1.23-2.33, P < 0.001) and poorer disease-free survival (DFS) (ES = 1.71, 95%CI = 1.11-2.31, P < 0.001). Disease-stratified analyses yielded significantly different estimates of CTHRC1 levels in the majority of the subgroups (all P < 0.05). In conclusion, increased CTHRC1 expression is associated with advanced TNM stage, increased LN metastasis and tumor size, and decreased OS and DFS, indicating that CTHRC1 may be a biomarker for prognosis of cancer patients.
Subject(s)
Extracellular Matrix Proteins/biosynthesis , Neoplasms/genetics , Prognosis , Proteomics , Disease-Free Survival , Extracellular Matrix Proteins/genetics , Gene Expression Regulation, Neoplastic , Humans , Lymphatic Metastasis , Neoplasm Staging , Neoplasms/pathologyABSTRACT
Limited information on oocytes and fertilization prevents the efficient therapy of patients with infertility. The most important reason for this lack of understanding is a deficiency in research dedicated to oocytes and fertilization. Currently, we are concerned with the role of nutrition in the process of oocyte development to better understand the relationship between nutrition and infertility. The aim of this study was to explore the relationship between some exceptional materials and infertility to elucidate the role of these materials in oocyte development. We used proteomic analysis to identify numerous nutrition-related proteins in three developmental stages: the germinal vesicle stage, the metaphase II-arrested stage, and the fertilized oocyte-zygote stage. Specific proteins were abundantly expressed during the three stages. These proteins included astacin-like metalloendopeptidase, selenium-binding proteins, and other proteins involved in metabolic and signaling pathways. Other proteins were involved in the citrate cycle, the electron transport chain, the urea cycle, fatty acid metabolism, and the insulin signaling pathway. Almost all these proteins exhibited different expression levels in the three stages. The results of the present study provide a better understanding of the molecular mechanisms of early embryonic development and suggest new treatment methods for infertility.
Subject(s)
Embryonic Development/genetics , Oocytes/growth & development , Protein Biosynthesis/genetics , Proteomics , Animals , Female , Fertilization in Vitro , Gene Expression Regulation, Developmental , Humans , Meiosis/genetics , Mice , Oocytes/metabolism , Oogenesis/genetics , Pregnancy , Reproduction/genetics , Signal Transduction , Zygote/growth & developmentABSTRACT
Parathyroid hormone-related protein (PTHrP) is involved in the deposition of milk calcium in mammal lactation, but its role in buffalo is unclear. In this study, the full-length coding sequence of the water buffalo PTHrP gene was first isolated using reverse transcription-polymerase chain reaction. The protein was then subjected to molecular characterization using bioinformatic methods, and the tissue expression pattern was further assayed by semi-quantitative reverse-transcription polymerase chain reaction. The water buffalo PTHrP gene contains an open reading frame of 534 base pairs encoding a polypeptide of 177 amino acid residues, a theoretical molecular weight of 20.32 kDa, and an isoelectric point of 10.00. In addition, water buffalo PTHrP was predicted to contain a signal peptide, a typical hydrophobic region with no hydrophobic transmembrane regions, and to exert its function in the cell nucleus. A conserved domain of parathyroid superfamily from amino acids 34-114 was observed in the polypeptide. Sequence comparison and the phylogenetic analysis showed that the sequence of the water buffalo PTHrP protein shared high homology with that of other mammals, particularly cattle and goat. Among the 16 tissues examined, the PTHrP gene was only expressed in adipose tissue, placenta, uterine wall, hypophysis, and mammary gland tissue, but gene expression levels were higher in the uterus wall and adipose tissue. The results of this study suggest that the PTHrP gene plays an important role in the deposition of milk calcium of water buffalo.
Subject(s)
Buffaloes/genetics , DNA, Complementary/genetics , Gene Expression Profiling , Parathyroid Hormone-Related Protein/genetics , Amino Acid Sequence , Animals , Base Sequence , Buffaloes/metabolism , Cloning, Molecular , DNA, Complementary/chemistry , Female , Molecular Sequence Data , Parathyroid Hormone-Related Protein/classification , Parathyroid Hormone-Related Protein/metabolism , Phylogeny , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Sequence Homology, Amino AcidABSTRACT
Tuberous sclerosis complex is an autosomal-dominant heritable disease caused by mutations in the TSC1 and TSC2 genes. We studied a Chinese patient with sporadic tuberous sclerosis complex. The clinical features of this patient included epilepsy, hypomelanotic macules and angiofibromas on his back; a cranial CT scan showed subependymal nodules along the lateral walls of the lateral ventricles. The TSC1 and TSC2 genes were studied by PCR and direct sequencing of the entire coding region and exon-intron boundaries of these genes. A novel deletion mutation (c.1964delA) in the TSC1 gene exon 15 was identified, which was not present in his parents or 100 unrelated normal controls. This is the first report of this c.1964delA mutation of the TSC1 gene, associated with tuberous sclerosis complex, expanding the spectrum of TSC1 mutations that cause this disease.