• Title/Summary/Keyword: biomarker gene

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Inferring Relative Activity between Pathway and Downstream Genes to Classify Melanoma Cancer Progression

  • Jung, In-Kyung;Lee, Jung-Sul;Choi, Chul-Hee;Kim, Dong-Sup
    • Interdisciplinary Bio Central
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    • v.3 no.1
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    • pp.5.1-5.5
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    • 2011
  • Introduction: Many signal transduction pathways mediate cell's behavior by regulating expression level of involved genes. Abnormal behavior indicates loss of regulatory potential of pathways, and this can be attributed to loss of expression regulation of downstream genes. Therefore, function of pathways should be assessed by activity of a pathway itself and relative activity between a pathway and downstream genes, simultaneously. Results and Discussion: In this study, we suggested a new method to assess pathway's function by introducing concept of 'responsiveness'. The responsiveness was defined as a relative activity between a pathway itself and its downstream genes. The expression level of a downstream gene as a function of an upstream pathway activation characterizes disease status. In this aspect, by using the responsiveness we predicted potential progress in cancer development. We applied our method to predict primary and metastatic status of melanoma cancer. The result shows that the responsiveness-based approach achieves better performance than using gene or pathway information alone. The mean of ROC scores in the responsiveness-based approach was 0.90 for GSE7553 data set, increased more than 40% compared to a gene-based method. Moreover, identifying the abnormal regulatory patterns between pathway and its downstream genes provided more biologically interpretable information compared to gene or pathway based approaches.

Characterization of histone gene expression in sevenband grouper, Hyporthodus septemfasciatus against nervous necrosis virus infection

  • Lee, Dong-Ryun;Lee, A-Reum;Krishnan, Rahul;Jang, Yo-Seb;Oh, Myung-Joo;Kim, Jong-Oh
    • Journal of fish pathology
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    • v.35 no.1
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    • pp.121-128
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    • 2022
  • Recent studies revealed that histone proteins are involved in innate immune responses during pathogen invasion as well as DNA packing. This study characterized the histone genes (H2A.V) of sevenband groupers and analyzed gene expression in NNV-infected sevenband groupers. The open reading frame (ORF) of H2A.V is 387 bp which encoded 128 amino acid residues. The deduced amino acid sequence of H2A.V harbor a highly conserved domain for H2A/H2B/H3 and H2A_C binding domain. Quantitative real-time PCR analysis showed that H2A.V had a high gene expression level in the brain and blood after being NNV-infected. An increase in extracellular histone protein in the blood has been identified as a biomarker for vascular function in humans. More research is required to understand histone's immune response at the protein level or in aquatic animals.

Identification of novel potential drugs and miRNAs biomarkers in lung cancer based on gene co-expression network analysis

  • Sara Hajipour;Sayed Mostafa Hosseini;Shiva Irani;Mahmood Tavallaie
    • Genomics & Informatics
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    • v.21 no.3
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    • pp.38.1-38.8
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    • 2023
  • Non-small cell lung cancer (NSCLC) is an important cause of cancer-associated deaths worldwide. Therefore, the exact molecular mechanisms of NSCLC are unidentified. The present investigation aims to identify the miRNAs with predictive value in NSCLC. The two datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEmiRNA) and mRNAs (DEmRNA) were selected from the normalized data. Next, miRNA-mRNA interactions were determined. Then, co-expression network analysis was completed using the WGCNA package in R software. The co-expression network between DEmiRNAs and DEmRNAs was calculated to prioritize the miRNAs. Next, the enrichment analysis was performed for DEmiRNA and DEmRNA. Finally, the drug-gene interaction network was constructed by importing the gene list to dgidb database. A total of 3,033 differentially expressed genes and 58 DEmiRNA were recognized from two datasets. The co-expression network analysis was utilized to build a gene co- expression network. Next, four modules were selected based on the Zsummary score. In the next step, a bipartite miRNA-gene network was constructed and hub miRNAs (let-7a-2-3p, let-7d-5p, let-7b-5p, let-7a-5p, and let-7b-3p) were selected. Finally, a drug-gene network was constructed while SUNITINIB, MEDROXYPROGESTERONE ACETATE, DOFETILIDE, HALOPERIDOL, and CALCITRIOL drugs were recognized as a beneficial drug in NSCLC. The hub miRNAs and repurposed drugs may act a vital role in NSCLC progression and treatment, respectively; however, these results must validate in further clinical and experimental assessments.

Long noncoding RNA involvement in cancer

  • Maruyama, Reo;Suzuki, Hiromu
    • BMB Reports
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    • v.45 no.11
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    • pp.604-611
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    • 2012
  • Recent advances in genome and transcriptome analysis have enabled identification of numerous members of a new class of noncoding RNA, long noncoding RNA (lncRNA). lncRNAs are broadly defined as RNA molecules greater than 200 nt in length and lacking an open reading frame. Recent studies provide evidence that lncRNAs play central roles in a wide range of cellular processes through interaction with key component proteins in the gene regulatory system, and that alteration of their cell- or tissue-specific expression and/or their primary or secondary structures is thought to promote cell proliferation, invasion and metastasis. The biological and molecular characteristics of the large majority of lncRNAs remains unknown, and it is anticipated that improved understanding of the roles played by lncRNAs in cancer will lead to the development of novel biomarkers and effective therapeutic strategies.

The Expression of Hsp70 and GST Genes in Mytilus coruscus during Air Exposure and Starvation (공기노출 및 절식시기 동안 참담치, Mytilus coruscus 에서 Hsp70 및 GST 유전자 발현에 대한 연구)

  • Kim, Chul Won;Kang, Han Seung
    • The Korean Journal of Malacology
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    • v.32 no.2
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    • pp.73-81
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    • 2016
  • Heat shock proteins (HSPs), one of the most highly conserved groups of proteins characterized to date, play crucial roles in protecting cells against environmental stresses, such as heat shock, salinity and oxidative stress. The glutathione S-transferases (GST) have important role in detoxification of oxidative stress, environmental chemicals and environmental stress. GST mRNA expression have been used as biomarkers on environmental stress. The purpose of this study was to investigate the death rate and the gene expression of Hsp70 and GST during air exposure and starvation. Results showed that, the expression of Hsp70 mRNA was significantly changed in the experiment groups, such as air exposure and starvation. GST mRNA expression was significantly increased in the experimental group of starvation. These results suggest that Hsp70 and GST were played roles in biomarker gene on the air exposure and starvation.

microRNA biomarkers in cystic diseases

  • Woo, Yu Mi;Park, Jong Hoon
    • BMB Reports
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    • v.46 no.7
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    • pp.338-345
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    • 2013
  • microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting the 3'-untranslated region of multiple target genes. Pathogenesis results from defects in several gene sets; therefore, disease progression could be prevented using miRNAs targeting multiple genes. Moreover, recent studies suggest that miRNAs reflect the stage of the specific disease, such as carcinogenesis. Cystic diseases, including polycystic kidney disease, polycystic liver disease, pancreatic cystic disease, and ovarian cystic disease, have common processes of cyst formation in the specific organ. Specifically, epithelial cells initiate abnormal cell proliferation and apoptosis as a result of alterations to key genes. Cysts are caused by fluid accumulation in the lumen. However, the molecular mechanisms underlying cyst formation and progression remain unclear. This review aims to introduce the key miRNAs related to cyst formation, and we suggest that miRNAs could be useful biomarkers and potential therapeutic targets in several cystic diseases.

Detection of Mycoplasma Infection in Cultured Cells on the Basis of Molecular Profiling of Host Responses

  • Chung, Tae Su;Kim, Ju Han;Lee, Young-Ju;Park, Woong-Yang
    • Genomics & Informatics
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    • v.3 no.3
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    • pp.63-67
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    • 2005
  • Adaptive responses to diverse microbial pathogens might be limited in relatively few types. Host cell responses to pathogens are believed to be patterned or stereotyped along with species or class. We tried to compose the host response to Mycoplasma in terms of cellular gene expression. Although gene expression profile of two host HeLa and 293 cells were quite different each other, 30 genes were differentially expressed by mycoplasma infection in both of HeLa and 293 cells. Six of them (PR48, MADH4, MKPX, CRK, RBM7, NEK3) were related to cell cycle or proliferation. Another category of genes like IL1 HY1, KLRF1, TNFSF14, GBP1 were host defense to elicit immune responses. With this set of genes, we establish the prediction model for mycoplasma contamination.

Comparative Microbiome Analysis of and Microbial Biomarker Discovery in Two Different Fermented Soy Products, Doenjang and Ganjang, Using Next-generation Sequencing (차세대 염기서열 분석법을 이용한 된장과 간장의 미생물 분포 및 바이오마커 분석)

  • Ha, Gwangsu;Jeong, Ho Jin;Noh, Yunjeong;Kim, JinWon;Jeong, Su-Ji;Jeong, Do-Youn;Yan, Hee-Jong
    • Journal of Life Science
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    • v.32 no.10
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    • pp.803-811
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    • 2022
  • Despite the importance of traditional Korean fermented foods, little is known about the microbial communities and diversity of fermented soy products. To gain insight into the unexplored microbial communities of both Doenjang (DJ) and Ganjang (GJ) that may contribute to the fermentation in Korean traditional foods, we carried out next-generation sequencing (NGS) based on the V3-V4 region of 16S rDNA gene analysis. The alpha diversity analysis results revealed that both the Shannon and Simpson diversity indices were significantly different between the two groups, whereas the richness indices, including ACE, CHAO, and Jackknife, were not significant. Firmicutes were the most dominant phylum in both groups, but several taxa were found to be more abundant in DJ than in GJ. The proportions of Bacillus, Kroppenstedtia, Clostridium, and Pseudomonas and most halophiles and halotolerant bacteria, such as Tetragenococcus, Chromohalobacter, Lentibacillus, and Psychrobacter, were lower in DJ than in GJ. Linear discriminant effect size (LEfSe) analysis was carried out to discover discriminative functional biomarkers. Biomarker discovery results showed that Bacillus and Tetragenococcus were identified as the most important features for the classification of subjects to DJ and GJ. Paired-permutational multivariate analysis of variance (PERMANOVA) further revealed that the bacterial community structure between the two groups was statistically different (p=0.001).

Intragenic DNA Methylation Concomitant with Repression of ATP4B and ATP4A Gene Expression in Gastric Cancer is a Potential Serum Biomarker

  • Raja, Uthandaraman Mahalinga;Gopal, Gopisetty;Rajkumar, Thangarajan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5563-5568
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    • 2012
  • Based on our previous report on gastric cancer which documented ATP4A and ATP4B mRNA down-regulation in gastric tumors relative to normal gastric tissues, we hypothesized that epigenetic mechanisms could be responsible. ATP4A and ATP4B mRNA expression in gastric cancer cell lines AGS, SNU638 and NUGC-3 was examined using reverse transcriptase PCR (RT-PCR). AGS cells were treated with TSA or 5'-AzaDC and methylation specific PCR (MSP) and bisulfite sequencing PCR (BSP) analysis were performed. MSP analysis was on DNA from paraffin embedded tissues sections and plasma. Expression analysis revealed downregulation of ATP4A and ATP4B genes in gastric cancer cell lines relative to normal gastric tissue, while treatment with 5'-AzaDC re-activated expression of both. Search for CpG islands in their putative promoter regions did not indicate CpG islands (CGI) but only further downstream in the bodies of the genes. Methylation specific PCR (MSP) in the exon1 of the ATP4B gene and exon7 in ATP4A indicated methylation in all the gastric cancer cell lines tested. MSP analysis in tumor tissue samples revealed methylation in the majority of tumor samples, 15/19, for ATP4B and 8/8 for ATP4A. There was concordance between ATP4B and ATP4A down-regulation and methylation status in the tumour samples tested. ATP4B methylation was detectable in cell free DNA from gastric cancer patient's plasma samples. Thus ATP4A and ATP4B down-regulation involves DNA methylation and methylated ATP4B DNA in plasma is a potential biomarker for gastric cancer.

Involvement of CELSR3 Hypermethylation in Primary Oral Squamous Cell Carcinoma

  • Khor, Goot Heah;Froemming, Gabrielle Ruth Anisah;Zain, Rosnah Binti;Abraham, Thomas Mannil;Lin, Thong Kwai
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.1
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    • pp.219-223
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    • 2016
  • Background: Promoter hypermethylation is a frequent epigenetic mechanism for gene transcription repression in cancer and is one of the hallmarks of the disease. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) contributes to cell contact-mediated communication. Dysregulation of promoter methylation has been reported in various cancers. Objectives: The objectives of this study were to investigate the CELSR3 hypermethylation level in oral squamous cell carcinomas (OSCCs) using methylation-sensitive high-resolution melting analysis (MS-HRM) and to correlate CELSR3 methylation with patient demographic and clinicopathological parameters. Materials and Methods: Frozen tissue samples of healthy subjects' normal mucosa and OSCCs were examined with regard to their methylation levels of the CELSR3 gene using MS-HRM. Results: MS-HRM analysis revealed a high methylation level of CELSR3 in 86% of OSCC cases. Significant correlations were found between CELSR3 quantitative methylation levels with patient ethnicity (P=0.005), age (P=0.024) and pathological stages (P=0.004). A moderate positive correlation between CELSR3 and patient age was also evident (R=0.444, P=0.001). Conclusions: CELSR3 promoter hypermethylation may be an important mechanism involved in oral carcinogenesis. It may thus be used as a biomarker in OSCC prognostication.