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Detecting robust gene signature through integrated analysis of multiple types of high-throughput data in liver cancer

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Acta Pharmacologica Sinica 2007年第12期28卷 2005-2010页

作者： Xin-yu ZHANG~(2,3,4,6),Tian-tian LI~(5,6),Xiang-jun LIU~(2,3,4,7)~2 department of Biological Science and Biotechnology,~3 School of Biomedicine and ~4 Ministry of Education Key laboratory of Bioinformatics,Tsinghua university Beijing 100084,china ~5 laboratory of medical genetics,department of biology,harbin medical university,harbin150086.china department of Biological Science and Biotechnology Tsinghua University Beijing China School of Biomedicine Tsinghua University Beijing China Ministry of Education Key laboratory of Bioinformatics Tsinghua University Beijing China department of biology Laboratory of Medical Genetics Harbin Medical University Harbin China

Aim:To investigate the robust gene signature in liver cancer,we applied anintegrated approach to perform a joint analysis of a highly diverse collection ofliver cancer genome-wide datasets,including genomic alterations and transcrip-tion ***:1-class Significance Analysis of Microarrays coupled withranking score method were used to identify the robust gene signature in livertumor ***:In total,1 625 051 gene expression measurements from 16public microarrays,2 pairs of serial analyses of gene expression experiments,and252 loss of heterozygosity reports obtained from 568 publications were used inthis integrated *** resulting robust gene signatures included 90 genes,which may be of great importance to liver cancer research.A system assessmentanalysis revealed that our integrative method had an accuracy of 92% and acorrelation coefficient value of ***:The system assessment resultsindicated that our method had the ability of integrating the datasets from varioustypes of sources,and eliciting more accurate results,as can be very useful in thestudy of liver cancer.

关键词： liver cancer integrated analysis robust gene signature gene expression map microarray SAGE

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Experimental Study of Rat Beta Islet Cells Cultured under Simulated Microgravity Conditions

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Acta Biochimica et Biophysica Sinica 2004年第1期36卷 47-50页

作者： Chun SONG, Xiu-Qing DUAN, Xi LI, Li-Ou HAN, Ping XU, Chun-Fang SONG, and Lian-Hong JIN (Key laboratory of Cell Transplantation of Ministry of Health, First Affiliated Hospital of harbin medical university, harbin 150001, china department of General Surgery, First Affiliated Hospital of harbin medical university, harbin 150001, china National Key laboratory of harbin Veterinary Research Institute of Chinese Agriculture Academy, harbin 150001, china Tissue Engineering Research Center, Histology and Embryology Staff Room, harbin medical university, harbin 150086, china ) Key laboratory of Cell Transplantation of Ministry of Health First Affiliated Hospital of Harbin Medical University Harbin 150001 China department of General Surgery First Affiliated Hospital of Harbin Medical University Harbin 150001 China National Key laboratory of harbin Veterinary Research Institute of Chinese Agriculture Academy harbin 150001 China Tissue Engineering Research Center Histology and Embryology Staff Room Harbin Medical University Harbin 150086 China

To observe the effects of simulated microgravity on beta islet cell culture, we have compared the survival rates and the insulin levels of the isolated rat islet cells cultured at micro- and normal gravity conditions. The survival rates of the cells cultured were determined by acridine orange-propidium iodide double-staining on day 3, 7 and 14. The morphology of the cells was observed by electron microscopy. Insulin levels were measured by radio immuno assays. Our results show that the cell number cultured under the microgravity condition is significantly higher than that under the routine condition (P<0.01). Some tubular structure shown by transmission electron microscopy, possibly for the transport of nutrients, were formed intercellularly in the microgravity cultured group on day 7. There were also abundant secretion particles and mitochondria in the cytoplasm of the cells. Scanning electron microscopy showed that there were holes formed between each islet, possibly connecting with the nutrient trans

关键词： simulated microgravity islet cell electron microscopy radioimmunoassay

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Genetic polymorphism and mRNA levels of cytochrome P450ⅡE1 and glutathione S-transferase P1 in patients with alcoholic liver disease in different nationalities

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Hepatobiliary & Pancreatic Diseases International 2009年第2期8卷 162-167页

作者： Ying Liu,Xiang-Wei Meng,Ling-Yun Zhou,Pei-Yi Zhang,Xun Sun and Ping Zhang department of Gastroenterology,First Affiliated Hospital,Jilin university,Changchun 130021,china department of Gastroenterology,Heilongjiang Province Hospital,harbin 150036,china department of medical Molecular biology,harbin medical university,harbin 150086,china department of Gastroenterology First Affiliated Hospital Jilin University Changchun 130021 China.

BACKGROUND:Alcohol abuse and dependence are major factors in the pathogenesis of alcoholic liver disease(ALD).Alcohol abuse is becoming an increasingly severe problem among the Han,Mongol,and Korean nationalities in northeast *** study aimed to investigate the relationship between ALD and the genetic polymorphism and expression levels of two enzymes,cytochrome P450ⅡE1(CYPⅡE1)and glutathione S-transferase P1(GSTP1)in patients of three ***:Peripheral blood was collected from 353 Chinese patients with ALD,300 alcohol dependent patients without liver disease(alcoholic),and 360 healthy *** group included patients from the Han,Mongol and Korean ***-time polymerase chain reaction(PCR)and PCR-restriction fragment length polymorphism(PCR-RFLP)were ***:Regardless of nationality,patients who carried the rare CYPⅡE1 C2 and GSTP1 Val alleles were at higher risk of *** frequency of C2 and Val in patients with ALD was respectively 50.00%and 26.98%in the Han,31.36%and 22.87%in the Mongol,and 45.87%and 22.02% in the Korean *** significant differences were seen in the frequency of either C2 or Val alleles in ALD patients among the three *** each nationality,the frequency of both C2 and Val alleles was significantly higher in ALD compared to alcoholic and healthy *** for nationality,the average mRNA levels of CYPⅡ E1 in ALD patients and healthy controls were 10.05%and 2.21%,*** average mRNA levels of GSTP1 in ALD patients and healthy controls were 0.53%and 2.12%,*** mRNA level of CYPⅡE1 was higher,and that of GSTP1 was lower in patients with ALD compared to the ***:Except for nationality,patients with ALD in this series tended to have a higher mRNA expression of CYPⅡE1 and to carry the C2 allele,and tended to have a lower mRNA expression of GSTP1 and to carry the Val *** is a causal relationship between the polymorphic alleles,which lea

关键词： alcoholic liver disease alcoholic genetic polymorphism mRNA expression

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Impaired PI3K/Akt signal pathway and hepatocellular injury in high-fat fed rats

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World Journal of Gastroenterology 2010年第48期16卷 6111-6118页

作者： Ji-Wu Han,department of Gastroenterology,The 4th Hospital of harbin medical university,harbin 150001,Heilongjiang Province,china Xiao-Rong Zhan,Xin-Yu Li,Bing Xia,Yue-Ying Wang,Jing Zhang,department of Endocrinology,First Hospital of harbin medical university,harbin 150001,Heilongjiang Province,china Bao-Xin Li,department of Pharmacology,State Key laboratory of Biomedicine and Pharmacology,harbin medical university,harbin 150001,Heilongjiang Province,china department of Endocrinology First Hospital of Harbin Medical University Harbin 150001 Heilongjiang Province China.

AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models of nonalcoholic fatty liver were established by high-fat diet feeding. The expression of total and phosphorylated P13K and Akt proteins in hepatocytes was determined by Western blotting. Degree of fat accumulation in liver was measured by hepatic triglyceride. Mitochondrial number and size were determined using quantitative morphometric analysis under transmission electron microscope. The permeability of the outer mitochondrial membrane was assessed by determining the potential gradient across this ***:After Wistar rats were fed with high-fat diet for 16 wk,their hepatocytes displayed an accumulation of fat (103.1 ± 12.6 vs 421.5 ± 19.7,P 5),and a reduction in the mitochondrial membrane potential (389.385% ± 18.612% vs 249.121% ± 13.526%,P 5). In addition,the expression of the phosphorylated P13K and Akt proteins in hepatocytes was reduced,as was the expression of the anti-apoptotic protein Bcl-2,while expression of the pro-apoptotic protein caspase-3 was increased. When animals were treated with pharmacological inhibitors of P13K or Akt,instead of high-fat diet,a similar pattern of hepatocellular fat accumulation,mitochondrial impairment,and change in the levels of PI3K,Akt,Bcl-2 was observed. CONCLUSION:High-fat diet appears to inhibit the PI3K/Akt signaling pathway,which may lead to hepa-tocellular injury through activation of the mitochondrial membrane pathway of apoptosis.

关键词： Nonalcoholic fatty liver Phosphatidylinositol 3-kinase/protein kinase B signaling pathway Mitochondria B-cell lymphoma gene 2 Caspase-3

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Cell cycle-dependent gene networks relevant to cancer

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Progress in Natural Science:Materials International 2008年第8期18卷 945-952页

作者： Yun Xiao a,1, Xia Lia,b,*,1, Yueying Yang a, Yadong Wangc, Shaoqi Rao a,b a College of Bioinformatics Science and Technology, and Bio-pharmaceutical Key laboratory of Heilongjiang Province and State, harbin medical university, harbin 150086, china b Biomedical Engineering Institute of Capital medical university, Beijing 10004, china c department of Computer Science, harbin Institute of Technology, harbin 150080, china College of Bioinformatics Science and Technology and Bio-pharmaceutical Key Laboratory of Heilongjiang Province and State Harbin Medical University Harbin 150086 China Biomedical Engineering Institute of Capital medical university Beijing 10004 China department of Computer Science Harbin Institute of Technology Harbin 150080 China

The analysis of sophisticated interplays between cell cycle-dependent genes in a disease condition is one of the largely unexplored areas in modern tumor biology research. Many cell cycle-dependent genes are either oncogenes or suppressor genes, or are closely associated with the transition of a cell cycle. However, it is unclear how the complicated relationships between these cell cycle-dependent genes are, especially in cancers. Here, we sought to identify significant expression relationships between cell cycle-dependent genes by analyzing a HeLa microarray dataset using a local alignment algorithm and constructed a gene transcriptional network specific to the cancer by assembling these newly identified gene-gene relationships. We further characterized this global network by partitioning the whole network into several cell cycle phase-specific sub-networks. All generated networks exhibited the power-law node-degree distribution, and the average clustering coefficients of these networks were remarkably higher than those of pure scale-free networks, indicating a property of hierarchical modularity. Based on the known protein-protein interactions and Gene Ontology annotation data, the proteins encoded by cell cycle-dependent interacting genes tended to share the same biological functions or to be involved in the same biological processes, rather than interacting by physical means. Finally, we identified the hub genes related to cancer based on the topological importance that maintain the basic structure of cell cycle-dependent gene networks.

关键词： Cell cycle Microarray HeLa cell Gene network

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Chinese Clinical Practice Guidelines for the Prevention and Treatment of Mother-to-Child Transmission of Hepatitis B Virus(Version 2024)

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Infectious Microbes & Diseases 2024年第3期6卷 108-116页

作者： Jinfeng Liu Qinglei Zeng Fanpu Ji Hong Ren Wenhong Zhang Lanjuan Li Yingren Zhao Infectious Diseases Physicians Branch of Chinese medical Doctor Association Chinese Society of Infectious Diseases of Chinese medical Association The First Affiliated Hospital of Xi’an Jiaotong university Xi’anChina Shaanxi Clinical medical Research Center of Infectious Diseases Xi’anChina The First Affiliated Hospital of Zhengzhou university ZhengzhouChina The Second Affiliated Hospital of Xi’an Jiaotong university Xi’anChina The Second Affiliated Hospital of Chongqing medical university ChongqingChina Huashan Hospital Fudan UniversityShanghaiChina State Key laboratory for the Diagnosis and Treatment of Infectious Diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina 不详

The Chinese Clinical Practice Guidelines for the prevention and treatment ofmother-to-child transmission of hepatitis B virus,developed by the Chinese Society of Infectious Diseases of the Chinese medical Association in 2019,serves as a valuable reference for standardizing the process of preventing mother-to-child transmission in *** new evidence emerges,it is crucial that timely and regular updates are made to the clinical practice guidelines so as to optimize guidance for clinical practice and *** this end,the Infectious Disease Physician Branch of Chinese medical Doctor Association and the Chinese Society of Infectious Diseases of Chinese medical Association,in collaboration with multidisciplinary experts,have updated the guidelines based on the latest domestic and international research advancements and clinical practice,in order to provide guidance and reference for clinicians andmaternal and child healthcare workers.

关键词： guidelines hepatitis B virus mother-to-child transmission prevention treatment update

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microRNA-181b targets MLK2 in HL-60 cells

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Science china(Life Sciences) 2010年第1期53卷 101-106页

作者： CHEN Hong1,CHEN Qun2,FANG Ming3 & MI Yan1 1 The First Affiliated Hospital of harbin medical university,harbin 150101,china 2 harbin Acheng District People’s Hospital,harbin 150300,china 3 Graduate department of harbin medical university,harbin 150001,china The First Affiliated Hospital of harbin medical university Harbin China harbin Acheng District People’s Hospital Harbin China Graduate department of harbin medical university Harbin China

microRNAs(miRNAs) play critical roles in many different cellular processes,including metabolism,apoptosis,differentiation and *** showed miR-181b to be highly expressed in acute myeloid leukemia(AML).Furthermore,miR-181b contributed to proliferation of AML cells by targeting *** results demonstrated that miR-181b plays an important role in the biology of AML and may be useful in developing therapies targeting miRNAs.

关键词： microRNA-181b MLK2 AML HL-60 proliferation apoptosis

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Heat Shock Protein 90 Indirectly Regulates ERK Activity by Affecting Raf Protein Metabolism

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Acta Biochimica et Biophysica Sinica 2005年第7期37卷 501-505页

作者： Fei DOU Liu-Di YUAN Jing-Jing ZHU department of genetics and Development biology,Southeast university medical School,Nanjing 210009,china department of genetics and Development biology Southeast University Medical SchoolNanjing 210009 China

Extracellular signal-regulated protein kinase (ERK) has been implicated in the pathogenesis ofseveral nerve system *** more and more kinases have been discovered to be the client proteins ofthe molecular chaperone Hsp90,the use of Hsp90 inhibitors to reduce abnormal kinase activity is a newtreatment strategy for nerve system *** study investigated the regulation of the ERK pathway *** showed that Hsp90 inhibitors reduce ERK phosphorylation without affecting the total ERKprotein *** investigation showed that Raf,the UPstream kinase in the Ras-Raf-MEK-ERK pathway,forms a complex with Hsp90 and *** cells with Hsp90 inhibitors facilitates Raf degradation,thereby down-regulating the activity of ERK.

关键词： molecular chaperone phosphorylation Hsp90 extracellular signal-regulated protein kinase (ERK) Raf tau

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Interaction of cellular-localized signature modules in response to prostate cancer

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Progress in Natural Science:Materials International 2007年第11期17卷 1368-1375页

作者： Zhu Jing1, Guo Zheng1,2, Zhang Min2, Yang Da2, Wang Jing2 and Wang Chenguang2(1. School of Life Science and Bioinformatics Centre, university of Electronic Science and Technology of china, Chengdu 610054, china 2. department of Bioinformatics, Bio-Pharmaceutical Key laboratory of Heilongjiang Province, harbin medical university, harbin 150081, china) School of Life Science and Bioinformatics Centre University of Electronic Science and Technology of China Chengdu 610054 China Bio-Pharmaceutical Key laboratory of Heilongjiang Province Department of Bioinformatics Harbin Medical University Harbin 150081 China

Rapid progress in high-throughput biotechnologies (e.g. microarrays) and exponential accumulation of gene functional knowledge makes it promising for systematic understanding of complex human diseases at the functional modules level. Current modular categorizations can be defined and selected more specifically and precisely in terms of both biological processes and cellular locations, aiming at uncovering the modular molecular networks highly relevant to cancers. Based on Gene Ontology, we identifed the functional modules enriched with differentially expressed genes and characterized by biological processes and specific cellular locations. Then, according to the ranking of the disease discriminating abilities of the pre-selected functional modules, we further defined and filtered signature modules which have higher relevance to the cancer under study. Applications of the proposed method to the analysis of a prostate cancer dataset revealed insightful biological modules.

关键词： microarray analysis Gene Ontology classification analysis cellular location functional module

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Intergrin gene expression profiles of human hepatocellular carcinoma

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World Journal of Gastroenterology 2002年第4期8卷 631-637页

作者： Lian-Xin Liu Hong-Chi Jiang Wei-Hui Zhang An-Long Zhu department of Surgery,the First Clinical College,harbin medical university,harbin 150001,Heilongjiang Province,china Lian-Xin Liu Zhi-Hua Liu Jing Zhou Xiu-Qin Wang Min Wu National laboratory of Molecular Oncology,department of Cell biology,Cancer Institute,Chinese Academy of medical Science & Peking Union medical College,Beijing 100021,china Cancer Institute Chinese Academy of Medical Science Peking Union Medical College Chaoyang District Beijing 100021 China

AIM: To investigate gene expression profiles of intergringenes in hepatocellular carcinoma (HCC) through theusage of Atlas Human Cancer Array membranes, semi-quantitative reverse transcription polymerase chainreaction (RT-PCR) and Northern ***: Hybridization of cDNA array membrane wasperformed with α 32P-labeled cDNA probes synthesizedfrom RNA isolated from hepatocellular carcinoma andadjacent non-cirrhotic liver. AtlasImage, which is asoftware specific to array, was used to analyze theresult. RT-PCR of 24 pairs specimen and Northern blotof 4 pairs specimen were used to confirm the expressionpattern of some intergrin genes identified by Atlasarrays ***: Among 588 genes spotted in membrane, 17genes were related to intergrin. Four genes were up-regulated, such as intergrin alpha8, beta1, beta7 andbeta8 in HCC. Whereas there were no genes down-regulated in HCC. RT-PCR and Northern blot analysisof intergrin beta1 gene gave results consistent withcDNA array ***: Investigation of these intergrin genesshould help to disclose the molecular mechanism of thecell adhesion, invasive and metastasis of HCC. A fewgenes are reported to have changed in HCC for the firsttime. The quick and high-throughout method of profilinggene expression by cDNA array provides us overviewof key factors that may involved in HCC, and may findthe clue of the study of HCC metastasis and moleculartargets of anti-metastasis therapy. The preciserelationship between the altered genes and HCC is amatter of further investigation.

关键词：肝癌整合素基因表达 RT-PCR 作用机制

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