1.Identification of prognosis-related key genes in hepatocellular carcinoma based on bioinformatics analysis.
Qian XIE ; Yingshan ZHU ; Ge HUANG ; Yue ZHAO
Journal of Central South University(Medical Sciences) 2025;50(2):167-180
OBJECTIVES:
Hepatocellular carcinoma is one of the most common primary malignant tumors with the third highest mortality rate worldwide. This study aims to identify key genes associated with hepatocellular carcinoma prognosis using the Gene Expression Omnibus (GEO) database and provide a theoretical basis for discovering novel prognostic biomarkers for hepatocellular carcinoma.
METHODS:
Hepatocellular carcinoma-related datasets were retrieved from the GEO database. Differentially expressed genes (DEGs) were identified using the GEO2R tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and key genes were identified using Cytoscape software. The University of Alabama at Birmingham Cancer Data Analysis Resource (UALCAN) was used to analyze the expression levels of key genes in normal and hepatocellular carcinoma tissues, as well as their associations with pathological grade, clinical stage, and patient survival. The Human Protein Atlas (THPA) was used to further validate the impact of key genes on overall survival. Expression levels of key genes in the blood of hepatocellular carcinoma patients were evaluated using the expression atlas of blood-based biomarkers in the early diagnosis of cancers (BBCancer).
RESULTS:
A total of 78 DEGs were identified from the GEO database. GO and KEGG analyses indicated that these genes may contribute to hepatocellular carcinoma progression by promoting cell division and regulating protein kinase activity. Sixteen key genes were screened via Cytoscape and validated using UALCAN and THPA. These genes were overexpressed in hepatocellular carcinoma tissues and were associated with disease progression and poor prognosis. Finally, BBCancer analysis showed that ASPM and NCAPG were also elevated in the blood of hepatocellular carcinoma patients.
CONCLUSIONS
This study identified 16 key genes as potential prognostic biomarkers for hepatocellular carcinoma, among which ASPM and NCAPG may serve as promising blood-based markers for hepatocellular carcinoma.
Humans
;
Carcinoma, Hepatocellular/mortality*
;
Liver Neoplasms/pathology*
;
Prognosis
;
Computational Biology/methods*
;
Protein Interaction Maps/genetics*
;
Biomarkers, Tumor/genetics*
;
Gene Expression Regulation, Neoplastic
;
Gene Expression Profiling
;
Gene Ontology
;
Databases, Genetic
2.Ferroptosis-related genes in osteoporosis: a bioinformatics analysis and in vitro study.
Yushuang XIA ; Bo WANG ; Pengfei PAN ; Xiangshun REN ; Lixi GAO ; Jian XIONG ; Yan MA
Journal of Zhejiang University. Medical sciences 2024;53(6):680-690
OBJECTIVES:
To explore ferroptosis-related genes in osteoporosis through bioinformatic analysis and in vitro study.
METHODS:
Osteoporosis-related genes were identified from dataset GSE35958 in the Gene Expression Omnibus database; and the ferroptosis-related genes were identified from the FerrDb database. These were intersected with the differentially expressed genes in GSE35958 to obtain ferroptosis-related genes in osteoporosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for the differentially expressed genes. And Spearman correlation and protein-protein interaction network analysis were performed. Then, the hub genes of ferroptosis in osteoporosis were screened by Degree, MNC, EPC, MCC and DMNC in Cytoscape software CytoHubba plugin; and analyzed with receiver operating characteristic (ROC) curves. The bone marrow mesenchymal stem cells from osteoporosis patients (osteoporosis group) and non-osteoporosis patients (control group) were subjected to quantitative reverse transcription polymerase chain reaction to detect the messenger RNA expression of ferroptosis hub genes in both groups.
RESULTS:
A total of 32 differentially expressed genes related to ferroptosis in osteoporosis were identified, including 26 up-regulated genes and 6 down-regulated genes. GO enrichment analysis showed that the identified genes were mainly involved in intercellular adhesion, lipid metabolism and cytokine response. KEGG enrichment analysis showed that the genes were mainly involved in signaling pathways of adhesive plaques, MAPK, PI3K-Akt, and Wnt. Spearman correlation analysis showed correlation among differentially expressed genes. Six hub genes for ferroptosis in osteoporosis were obtained, namely MAPK3, CDKN1A, MAP1LC3A, TNF, RELA, and TGF-β1. ROC curve analysis showed that these hub genes had good diagnostic performance in osteoporosis and may become potential biomarkers of osteoporosis. In vitro experiments confirmed significant differences in these hub genes between the control group and the osteoporosis group (all P<0.05).
CONCLUSIONS
This study has identified six ferroptosis-related hub genes in osteoporosis, which may be used as novel biomarkers for the early diagnosis and treatment of osteoporosis.
Osteoporosis/genetics*
;
Humans
;
Computational Biology
;
Ferroptosis/genetics*
;
Protein Interaction Maps/genetics*
;
Gene Ontology
;
Mesenchymal Stem Cells/metabolism*
;
Gene Expression Profiling
;
Databases, Genetic
3.Proteomics and peptidomics analysis of Sepiae Endoconcha.
Rui LIU ; Shuang WEI ; Xin-Zhi WANG ; Jian-Ming CHENG ; Hao WU
China Journal of Chinese Materia Medica 2020;45(16):3883-3889
Shotgun based proteomics and peptidomics analysis were used to investigate the proteins and peptides in marine traditional Chinese medicine(TCM) Sepiae Endoconcha(cuttlebone). Peptides were extracted from cuttlebone by acidified methanol, and then strong cation exchange(SCX) resin was used to enrich those peptides. Also, proteins from cuttlebone were extracted and digested by trypsin. nano-LC Q Exactive Orbitrap mass spectrometry was used to analyze proteins and peptides from cuttlebone. As a result, a total of 16 proteins and 168 peptides were identified by protein database search, and 328 peptides were identified by De novo sequencing. The identified proteins were hemocyanin, enolase, myosin, actin, calmodulin, etc., and the identified peptides were derived from actin, histone, and tubulin. All these proteins and peptides were important components in cuttlebone, which would provide important theoretical and research basis for marine TCM cuttlebone investigations.
Cations
;
Databases, Protein
;
Mass Spectrometry
;
Peptides
;
Proteomics
4.Re-evaluation of liver injury associated with Buguzhi Preparations based on passive monitoring data and hospital cases.
Ya-Lei LIU ; Fei-Lin GE ; Jing-Xiao ZHU ; Jing JING ; Jia-Bo WANG ; Ya-Ming ZHANG ; Yu-Ming GUO ; Xiao-He XIAO
China Journal of Chinese Materia Medica 2019;44(19):4272-4276
In this paper,the case reports on rug-induced liver injury( ADR cases) related to Gukang Capsules containing Psoralea corylifolia( Buguzhi,BGZ) were collected from the adverse reaction monitoring database from January 1,2012 to December 31,2016,and the in-patients cases with drug-induced liver injury admitted to a tertiary Class A liver disease hospital from January 1,2010 to December 31,2016 were also collected. These collected cases were re-evaluated and analyzed. 110 cases with liver injury related to this preparation were collected from adverse reaction monitoring database,and 55 cases of them received the preparation alone,mainly for fracture treatment( 52. 74%). Ninty one cases( 82. 72%) met the standard of the biochemical diagnostic criteria for drug-induced liver injury. 89. 01% of patients were over the age of 41 and women accounted for 60. 9%. The time from administration to liver injury was 1-208 days,with the median of 29 d. The dose of the preparation was 2. 4-4. 8 g per day,with a cumulative dose ranging from 3. 6-699. 6 g. The recovery and improvement rate reached 96. 70% after positive treatment. Seven inpatient cases related to the preparation were collected in a tertiary Class A liver disease hospital,6 females and 1 male. All of them were over 40 years old. Two cases reached the " suspicious diagnosis" standard and 5 cases reached the " clinical diagnosis" standard in Guidelines for the diagnosis and treatment of herb-induced liver injury. Six patients had a good prognosis effect,but another one had liver failure. This preparation is commonly used in fracture,osteoarthritis and other diseases,with remarkable curative effect. However,ADR cases and hospital cases all indicated the risk of liver injury. There was no significant correlation between the time and dose of drug use and the occurrence of liver injury.The induced-liver injury may have immunological heterogeneity,thus regular monitoring of liver function should be taken during clinical use.
Adult
;
Chemical and Drug Induced Liver Injury
;
Databases, Factual
;
Drugs, Chinese Herbal
;
Female
;
Humans
;
Male
5.Network pharmacological study of Schizonepetae Herba and Saposhnikoviae Radix in treatment of ulcerative colitis.
Ying QU ; Shu-Xin ZHANG ; Lu ZHOU ; Li-Yuan FU ; Zi-Hao LIU ; Shi-Ying LI ; Ting-Ting DAI ; Xiang-Yang YANG ; Hui-Ru JI ; Min-Ran CAO
China Journal of Chinese Materia Medica 2019;44(24):5465-5472
The aim of this paper was to screen the active targets of Schizonepetae Herba and Saposhnikoviae Radix in the treatment of ulcerative colitis by means of network pharmacology,and to investigate their mechanism of action. The effective components of Schizonepetae Herba and Saposhnikoviae Radix were screened out by traditional Chinese medicine systematic pharmacological( TCMSP)database,with oral bioavilability( OB) ≥30% and drug-like( DL) ≥18% selected as the thresholds. Target PPI network was built between the main components and their corresponding targets. One hundred and eighty-two human genes corresponding to the medicine target sites were obtained from Uniprot database; 3 874 genes corresponding to ulcerative colitis were obtained from Genecard database.A total of 115 intersection genes were screened from disease genes and medicine genes,and the PPI interaction analysis was conducted by using String tool. Disease-target PPI network was drawn by using Cytoscape software,and component-target-disease network was constructed. One hundred and eight nodes and 1 882 connections were found,and then Cytoscape software was used to merge the networks and filter the core network for gene GO function analysis and KEGG pathway enrichment analysis. The mechanism of Schizonepetae Herba and Saposhnikoviae Radix was then verified by animal experiment. Gene GO functional analysis suggested that biological process,molecular functions and cell components were involved,and it was found that ulcerative colitis might be related to transcription factor activity,and cytokine receptor binding,etc. Gene KEGG pathway enrichment analysis showed that the mechanism of ulcerative colitis might be associated with TNF and Toll-like receptors( TLRs) signaling pathway-mediated cytoinflammatory factors interleukin-1( IL-1) and interleukin-6( IL6). The possible mechanism of the effective components of Schizonepetae Herba and Saposhnikoviae Radix in treating ulcerative colitis might be related to intervening the cytokine receptor binding of TNF and TLRs signaling pathways,reducing the transcription of nuclear factor-kappaB( NF-κB),and inhibiting the secretion of intestinal inflammatory factors IL-1 and IL-6.
Animals
;
Apiaceae/chemistry*
;
Colitis, Ulcerative/drug therapy*
;
Databases, Genetic
;
Drugs, Chinese Herbal/therapeutic use*
;
Humans
;
Interleukins/metabolism*
;
Lamiaceae/chemistry*
;
Medicine, Chinese Traditional
;
Phytotherapy
;
Plant Roots/chemistry*
;
Protein Interaction Mapping
;
Signal Transduction
;
Software
;
Toll-Like Receptors/metabolism*
6.Molecular Detection of Coxiella burnetii in Cattle on Ulleung Island, Korea: A Population-based Study with Four Years of Follow Up
Min Goo SEO ; Oh Deog KWON ; Dongmi KWAK
The Korean Journal of Parasitology 2019;57(1):69-73
In a population-based study with 4 years of follow up, we evaluated the prevalence of Coxiella burnetii in cattle on Ulleung Island, Korea. In this study, the rates of C. burnetii infection in cattle on Ulleung Island were determined by PCR and were found to be 0.3–1.0% in the period 2011–2014. All 17 C. burnetii partial 16S rRNA gene sequences from PCR-positive cattle were identical and 2 geographic representatives were included in our analysis. The nucleotide sequences of the 2 samples showed high (98.4–100%) identity with C. burnetii sequences obtained from the GenBank. In this long-term tracking study, the number of cattle positive for C. burnetii on Ulleung Island was low. To prevent the transmission of C. burnetii on Ulleung Island, control strategy should include biosecurity improvement in surveillance, livestock management, administering suitable tests before purchasing animals to detect C. burnetii shedders, and restricting movements between herds.
Animals
;
Base Sequence
;
Cattle
;
Coxiella burnetii
;
Coxiella
;
Databases, Nucleic Acid
;
Follow-Up Studies
;
Genes, rRNA
;
Korea
;
Livestock
;
Phylogeny
;
Polymerase Chain Reaction
;
Prevalence
7.Cytochrome C Oxidase Subunit 1, Internal Transcribed Spacer 1, Nicotinamide Adenine Dinucleotide Hydrogen Dehydrogenase Subunits 2 and 5 of Clonorchis sinensis Ancient DNA Retrieved from Joseon Dynasty Mummy Specimens
Jong Ha HONG ; Chang Seok OH ; Jong Yil CHAI ; Min SEO ; Dong Hoon SHIN
Journal of Korean Medical Science 2019;34(20):e149-
We analyzed Clonorchis sinensis ancient DNA (aDNA) acquired from the specimens of the Joseon mummies. The target regions were cytochrome C oxidase subunit 1 (CO1), internal transcribed spacer 1 (ITS1), nicotinamide adenine dinucleotide hydrogen (NADH) dehydrogenase subunits 2 (NAD2) and 5 (NAD5). The sequences of C. sinensis aDNA was completely or almost identical to modern C. sinensis sequences in GenBank. We also found that ITS1, NAD2 and NAD5 could be good markers for molecular diagnosis between C. sinensis and the other trematode parasite species. The current result could improve our knowledge about genetic history of C. sinensis.
Clonorchis sinensis
;
Cytochromes c
;
Cytochromes
;
Databases, Nucleic Acid
;
Diagnosis
;
DNA
;
Electron Transport Complex IV
;
Hydrogen
;
Mummies
;
NAD
;
Niacinamide
;
Oxidoreductases
;
Parasites
;
Republic of Korea
8.Necessity of Guidelines for Research in Forensic Science: DNA Identification
Korean Journal of Legal Medicine 2019;43(2):54-63
Forensic science is an academic field that utilizes scientific knowledge and the conducting of research in legal procedures. Recently, legal science has been receiving more attention since the use of DNA identification started, especially in criminal procedures, in accordance with the development of human genetics. DNA identification has been used to identify criminals by analyzing humanoriginated biological materials obtained from crime scenes, and, more recently, the breadth and effectiveness of their use has been increasing with the operation of DNA databases. The Korean government regulates the operation and utilization of the DNA database through the “Act on Use and Protection of DNA Identification Information.” Meanwhile, the actual study of human genetics is regulated by the “Bioethics and Safety Act.” Professional areas, such as forensic science, are not areas where regulation by the laws is appropriate. However, the core part of behavior has to be ruled by the laws, considering the impact of scientific achievements on society and individuals when they are utilized. Since most scientific research and performance utilization belong in the scientific and technological domains, regulation through experts' autonomous guidelines is more appropriate. For the regulation of biomedical research through ethical guidelines, some requirements should be satisfied: the ethical guideline should be made by suitable professionals; the ethical guideline should be scientifically and ethically reliable; the ethical guideline should be enforced by a trustworthy institution; and most importantly, the scientist community should be trustworthy.
Crime
;
Criminals
;
Databases, Nucleic Acid
;
DNA
;
Forensic Sciences
;
Genetics, Medical
;
Humans
;
Jurisprudence
9.Molecular Prevalence of Cryptosporidium spp. in Breeding Kennel Dogs
Naoyuki ITOH ; Hazuki TANAKA ; Yuko IIJIMA ; Satoshi KAMESHIMA ; Yuya KIMURA
The Korean Journal of Parasitology 2019;57(2):197-200
Cryptosporidium is a common intestinal protozoan that can lead to diarrhea in humans and dogs. The predominant species of infection are C. hominis and C. parvum in humans, and C. canis in dogs. However, C. canis can infect immunocompromised humans. Considering the close contact with humans, dogs have the potential to be reservoirs for human cryptosporidiosis. Breeding kennels are the major supply source of puppies for pet shops. The present study is to determine the molecular prevalence and characteristics of Cryptosporidium spp. found in breeding kennel dogs. A total of 314 fecal samples were collected from young and adult dogs kept in 5 breeding kennels. A polymerase chain reaction targeting the small subunit rRNA gene was employed for the detection of Cryptosporidium spp. To determine the species, the DNA sequences were compared to GenBank data. Overall, 21.0% of the fecal samples were positive for Cryptosporidium spp. infection. Cryptosporidium spp. was detected in all 5 facilities. A sequencing analysis demonstrated that all isolates shared 99–100% similarity with C. canis. The results suggest that Cryptosporidium spp. infection is present at a high-level in breeding kennel dogs. However, because dominant species in this survey was C. canis, the importance of breeding kennel dogs as reservoirs for Cryptosporidium spp. transmission to humans is likely to be low in Japan.
Adult
;
Animals
;
Base Sequence
;
Breeding
;
Cryptosporidiosis
;
Cryptosporidium
;
Databases, Nucleic Acid
;
Diarrhea
;
Dogs
;
Genes, rRNA
;
Humans
;
Japan
;
Polymerase Chain Reaction
;
Prevalence
10.Mitochondrial DNA Sequence Variability of Spirometra Species in Asian Countries
Hyeong Kyu JEON ; Keeseon S EOM
The Korean Journal of Parasitology 2019;57(5):481-487
Mitochondrial DNA sequence variability of Spirometra erinaceieuropaei in GenBank was observed by reinvestigation of mitochondrial cox1 and cytb sequences. The DNA sequences were analyzed in this study, comprising complete DNA sequences of cox1 (n=239) and cytb (n=213) genes. The 10 complete mitochondrial DNA sequences of Spirometra species were compared with those of Korea, China and Japan. The sequences were analyzed for nucleotide composition, conserved sites, variable sites, singleton sites and parsimony-informative sites. Phylogenetic analyses was done using neighbor joining, maximum parsimony, Bayesian inference and maximum-likelihood on cox1 and cytb sequences of Spirometra species. These polymorphic sites identified 148 (cox1) and 83 (cytb) haplotypes within 239 and 213 isolates from 3 Asian countries. Phylogenetic tree topologies were presented high-level confidence values for the 2 major branches of 2 Spirometra species containing S. erinaceieuropaei and S. decipiens, and S. decipiens sub-clades including all sequences registered as S. erinaceieuropaei in cox1 and cytb genes. These results indicated that mitochondrial haplotypes of S. erinaceieuropaei and S. decipiens were found in the 3 Asian countries.
Asian Continental Ancestry Group
;
Base Sequence
;
China
;
Databases, Nucleic Acid
;
DNA, Mitochondrial
;
Haplotypes
;
Humans
;
Japan
;
Korea
;
Mitochondria
;
Spirometra
;
Trees

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