LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 23

Search options

  1. Article: The tumor multi-omic landscape of endometrial cancers developed on a germline genetic background of adiposity.

    Richenberg, George / Francis, Amy / Owen, Carina N / Gray, Victoria / Robinson, Timothy / Gabriel, Aurélie Ag / Lawrenson, Kate / Crosbie, Emma J / Schildkraut, Joellen M / Mckay, James D / Gaunt, Tom R / Relton, Caroline L / Vincent, Emma E / Kar, Siddhartha P

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: High body mass index (BMI) is a causal risk factor for endometrial cancer but the tumor molecular mechanisms affected by adiposity and their therapeutic relevance remain poorly understood. Here we characterize the tumor multi-omic landscape of ... ...

    Abstract High body mass index (BMI) is a causal risk factor for endometrial cancer but the tumor molecular mechanisms affected by adiposity and their therapeutic relevance remain poorly understood. Here we characterize the tumor multi-omic landscape of endometrial cancers that have developed on a background of lifelong germline genetic exposure to elevated BMI. We built a polygenic score (PGS) for BMI in women using data on independent, genome-wide significant variants associated with adult BMI in 434,794 women. We performed germline (blood) genotype quality control and imputation on data from 354 endometrial cancer cases from The Cancer Genome Atlas (TCGA). We assigned each case in this TCGA cohort their genetically predicted life-course BMI based on the BMI PGS. Multivariable generalized linear models adjusted for age, stage, microsatellite status and genetic principal components were used to test for associations between the BMI germline PGS and endometrial cancer tumor genome-wide genomic, transcriptomic, proteomic, epigenomic and immune traits in TCGA. High BMI germline PGS was associated with (i) upregulated tumor gene expression in the
    Language English
    Publishing date 2023-10-10
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.09.23296765
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Common genetic variations in telomere length genes and lung cancer: a Mendelian randomisation study and its novel application in lung tumour transcriptome.

    Cortez Cardoso Penha, Ricardo / Smith-Byrne, Karl / Atkins, Joshua R / Haycock, Philip C / Kar, Siddhartha / Codd, Veryan / Samani, Nilesh J / Nelson, Christopher / Milojevic, Maja / Gabriel, Aurélie A G / Amos, Christopher / Brennan, Paul / Hung, Rayjean J / Kachuri, Linda / Mckay, James D

    eLife

    2023  Volume 12

    Abstract: Background: Genome-wide association studies (GWASs) have identified genetic susceptibility variants for both leukocyte telomere length (LTL) and lung cancer susceptibility. Our study aims to explore the shared genetic basis between these traits and ... ...

    Abstract Background: Genome-wide association studies (GWASs) have identified genetic susceptibility variants for both leukocyte telomere length (LTL) and lung cancer susceptibility. Our study aims to explore the shared genetic basis between these traits and investigate their impact on somatic environment of lung tumours.
    Methods: We performed genetic correlation, Mendelian randomisation (MR), and colocalisation analyses using the largest available GWASs summary statistics of LTL (N=464,716) and lung cancer (N=29,239 cases and 56,450 controls). Principal components analysis based on RNA-sequencing data was used to summarise gene expression profile in lung adenocarcinoma cases from TCGA (N=343).
    Results: Although there was no genome-wide genetic correlation between LTL and lung cancer risk, longer LTL conferred an increased risk of lung cancer regardless of smoking status in the MR analyses, particularly for lung adenocarcinoma. Of the 144 LTL genetic instruments, 12 colocalised with lung adenocarcinoma risk and revealed novel susceptibility loci, including
    Conclusions: This study identified an association between longer genetically predicted LTL and lung cancer and sheds light on the potential molecular mechanisms related to LTL in lung adenocarcinomas.
    Funding: Institut National du Cancer (GeniLuc2017-1-TABAC-03-CIRC-1-TABAC17-022), INTEGRAL/NIH (5U19CA203654-03), CRUK (C18281/A29019), and Agence Nationale pour la Recherche (ANR-10-INBS-09).
    MeSH term(s) Humans ; Female ; Male ; Transcriptome ; Genome-Wide Association Study ; Risk Factors ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Adenocarcinoma of Lung/genetics ; Adenocarcinoma of Lung/metabolism ; Leukocytes/metabolism ; Telomere/genetics ; Telomere/metabolism ; Genetic Variation ; RNA Splicing Factors/metabolism ; Transcription Factors/metabolism
    Chemical Substances PRPF6 protein, human ; RNA Splicing Factors ; Transcription Factors
    Language English
    Publishing date 2023-04-20
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.83118
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article: Development of a custom next-generation sequencing panel for the determination of bladder cancer risk in a Tunisian cohort [Erratum: February 2022, v.49(2); p.1259]

    Hemissi, Imen / Boussetta, Sami / Dallali, Hamza / Hellal, Faycel / Durand, Geoffroy / Voegele, Catherine / Ayed, Haroun / Zaghbib, Selim / Naimi, Zeineb / Ayadi, Mouna / Chebil, Mohamed / Mckay, James / Le Calvez-Kelm, Florence / Ouerhani, Slah

    Molecular biology reports. 2022 Feb., v. 49, no. 2

    2022  

    Abstract: BACKGOUND: Bladder cancer (BCa) is a heterogeneous disease caused by the interaction between environmental and genetic risk factors. The goal of this case–control study was to evaluate the implication of a selected SNP panel in the risk of BCa ... ...

    Abstract BACKGOUND: Bladder cancer (BCa) is a heterogeneous disease caused by the interaction between environmental and genetic risk factors. The goal of this case–control study was to evaluate the implication of a selected SNP panel in the risk of BCa development in a Tunisian cohort. We were also interested in studying the interaction between this predictive panel and environmental risk factors. METHODS: The case/control cohort was composed with 249 BCa cases and 255 controls. The designed Bladder cancer hereditary panel (BCHP) was composed of 139 selected variants. These variants were genotyped by an amplification-based targeted Next-Generation Sequencing (NGS) on the Ion Torrent Proton sequencer (Life Technologies, Ion Torrent technology). RESULTS: We have found that rs162555, rs2228000, rs10936599, rs710521, rs3752645, rs804276, rs4639, rs4881400 and rs288980 were significantly associated with decreased risk of bladder cancer. However the homozygous genotypes for VPS37C (rs7104333, A/A), MPG (rs1013358, C/C) genes or the heterozygous genotype for ARNT gene (rs1889740, rs2228099, rs2256355, rs2864873), GSTA4 (rs17614751) and APOBR/IL27 (rs17855750) were significantly associated with increased risk of bladder cancer development compared to reference group (OR 2.53, 2.34, 1.99, 2.00, 2.00, 1.47, 1.96 and 2.27 respectively). We have also found that non–smokers patients harboring heterozygous genotypes for ARNT/rs2864873 (A > G), ARNT/ rs1889740 (C > T) or GSTA4/rs17614751 (G–A) were respectively at 2.775, 3.069 and 6.608-fold increased risk of Bca development compared to non-smokers controls with wild genotypes. Moreover the ARNT CT (rs1889740), ARNT CG (rs2228099), ARNT TC (rs2864873) and GSS GA genotypes were associated with an increased risk of BCa even in absence of professional risk factors. Finally the decision-tree analysis produced a three major BCa classes. These three classes were essentially characterized by an intensity of tobacco use more than 20 pack years (PY) and the CYP1A2 (rs762551) genotype. CONCLUSIONS: The determined association between environmental factors, genetic variations and the risk of Bca development may provide additional information to urologists that may help them for clinical assessment and treatment decisions. Nevertheless, the underlying mechanisms through which these genes or SNPs affect the clinical behavior of BCas require further studies.
    Keywords carcinogenesis ; case-control studies ; decision support systems ; genes ; genotyping ; heterozygosity ; homozygosity ; molecular biology ; risk reduction ; tobacco use ; urinary bladder neoplasms
    Language English
    Dates of publication 2022-02
    Size p. 1233-1258.
    Publishing place Springer Netherlands
    Document type Article
    ZDB-ID 186544-4
    ISSN 1573-4978 ; 0301-4851
    ISSN (online) 1573-4978
    ISSN 0301-4851
    DOI 10.1007/s11033-021-06951-4
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

  4. Article ; Online: Power analysis in a SMART design: sample size estimation for determining the best embedded dynamic treatment regime.

    Artman, William J / Nahum-Shani, Inbal / Wu, Tianshuang / Mckay, James R / Ertefaie, Ashkan

    Biostatistics (Oxford, England)

    2018  Volume 21, Issue 3, Page(s) 432–448

    Abstract: Sequential, multiple assignment, randomized trial (SMART) designs have become increasingly popular in the field of precision medicine by providing a means for comparing more than two sequences of treatments tailored to the individual patient, i.e., ... ...

    Abstract Sequential, multiple assignment, randomized trial (SMART) designs have become increasingly popular in the field of precision medicine by providing a means for comparing more than two sequences of treatments tailored to the individual patient, i.e., dynamic treatment regime (DTR). The construction of evidence-based DTRs promises a replacement to ad hoc one-size-fits-all decisions pervasive in patient care. However, there are substantial statistical challenges in sizing SMART designs due to the correlation structure between the DTRs embedded in the design (EDTR). Since a primary goal of SMARTs is the construction of an optimal EDTR, investigators are interested in sizing SMARTs based on the ability to screen out EDTRs inferior to the optimal EDTR by a given amount which cannot be done using existing methods. In this article, we fill this gap by developing a rigorous power analysis framework that leverages the multiple comparisons with the best methodology. Our method employs Monte Carlo simulation to compute the number of individuals to enroll in an arbitrary SMART. We evaluate our method through extensive simulation studies. We illustrate our method by retrospectively computing the power in the Extending Treatment Effectiveness of Naltrexone (EXTEND) trial. An R package implementing our methodology is available to download from the Comprehensive R Archive Network.
    MeSH term(s) Biomedical Research/methods ; Biomedical Research/standards ; Humans ; Models, Statistical ; Monte Carlo Method ; Naltrexone/pharmacology ; Outcome Assessment, Health Care/methods ; Randomized Controlled Trials as Topic/methods ; Randomized Controlled Trials as Topic/standards ; Research Design/standards ; Sample Size
    Chemical Substances Naltrexone (5S6W795CQM)
    Language English
    Publishing date 2018-10-23
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2031500-4
    ISSN 1468-4357 ; 1465-4644
    ISSN (online) 1468-4357
    ISSN 1465-4644
    DOI 10.1093/biostatistics/kxy064
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Correction to: Development of a custom next-generation sequencing panel for the determination of bladder cancer risk in a Tunisian cohort.

    Hemissi, Imen / Boussetta, Sami / Dallali, Hamza / Hellal, Faycel / Durand, Geoffroy / Voegele, Catherine / Ayed, Haroun / Zaghbib, Selim / Naimi, Zeineb / Ayadi, Mouna / Chebil, Mohamed / Mckay, James / Le Calvez-Kelm, Florence / Ouerhani, Slah

    Molecular biology reports

    2021  Volume 49, Issue 2, Page(s) 1259

    Language English
    Publishing date 2021-12-24
    Publishing country Netherlands
    Document type Published Erratum
    ZDB-ID 186544-4
    ISSN 1573-4978 ; 0301-4851
    ISSN (online) 1573-4978
    ISSN 0301-4851
    DOI 10.1007/s11033-021-07052-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Development of a custom next-generation sequencing panel for the determination of bladder cancer risk in a Tunisian cohort.

    Hemissi, Imen / Boussetta, Sami / Dallali, Hamza / Hellal, Faycel / Durand, Geoffroy / Voegele, Catherine / Ayed, Haroun / Zaghbib, Selim / Naimi, Zeineb / Ayadi, Mouna / Chebil, Mohamed / Mckay, James / Le Calvez-Kelm, Florence / Ouerhani, Slah

    Molecular biology reports

    2021  Volume 49, Issue 2, Page(s) 1233–1258

    Abstract: Backgound: Bladder cancer (BCa) is a heterogeneous disease caused by the interaction between environmental and genetic risk factors. The goal of this case-control study was to evaluate the implication of a selected SNP panel in the risk of BCa ... ...

    Abstract Backgound: Bladder cancer (BCa) is a heterogeneous disease caused by the interaction between environmental and genetic risk factors. The goal of this case-control study was to evaluate the implication of a selected SNP panel in the risk of BCa development in a Tunisian cohort. We were also interested in studying the interaction between this predictive panel and environmental risk factors.
    Methods: The case/control cohort was composed with 249 BCa cases and 255 controls. The designed Bladder cancer hereditary panel (BCHP) was composed of 139 selected variants. These variants were genotyped by an amplification-based targeted Next-Generation Sequencing (NGS) on the Ion Torrent Proton sequencer (Life Technologies, Ion Torrent technology).
    Results: We have found that rs162555, rs2228000, rs10936599, rs710521, rs3752645, rs804276, rs4639, rs4881400 and rs288980 were significantly associated with decreased risk of bladder cancer. However the homozygous genotypes for VPS37C (rs7104333, A/A), MPG (rs1013358, C/C) genes or the heterozygous genotype for ARNT gene (rs1889740, rs2228099, rs2256355, rs2864873), GSTA4 (rs17614751) and APOBR/IL27 (rs17855750) were significantly associated with increased risk of bladder cancer development compared to reference group (OR 2.53, 2.34, 1.99, 2.00, 2.00, 1.47, 1.96 and 2.27 respectively). We have also found that non-smokers patients harboring heterozygous genotypes for ARNT/rs2864873 (A > G), ARNT/ rs1889740 (C > T) or GSTA4/rs17614751 (G-A) were respectively at 2.775, 3.069 and 6.608-fold increased risk of Bca development compared to non-smokers controls with wild genotypes. Moreover the ARNT CT (rs1889740), ARNT CG (rs2228099), ARNT TC (rs2864873) and GSS GA genotypes were associated with an increased risk of BCa even in absence of professional risk factors. Finally the decision-tree analysis produced a three major BCa classes. These three classes were essentially characterized by an intensity of tobacco use more than 20 pack years (PY) and the CYP1A2 (rs762551) genotype.
    Conclusions: The determined association between environmental factors, genetic variations and the risk of Bca development may provide additional information to urologists that may help them for clinical assessment and treatment decisions. Nevertheless, the underlying mechanisms through which these genes or SNPs affect the clinical behavior of BCas require further studies.
    MeSH term(s) Aged ; Aged, 80 and over ; Case-Control Studies ; Cohort Studies ; Female ; Gene Expression/genetics ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic/genetics ; Genetic Predisposition to Disease/genetics ; Genetic Testing/methods ; Genotype ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; Risk Factors ; Transcriptome/genetics ; Tunisia/epidemiology ; Urinary Bladder/pathology ; Urinary Bladder Neoplasms/diagnosis ; Urinary Bladder Neoplasms/genetics
    Language English
    Publishing date 2021-12-01
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 186544-4
    ISSN 1573-4978 ; 0301-4851
    ISSN (online) 1573-4978
    ISSN 0301-4851
    DOI 10.1007/s11033-021-06951-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: TP53

    Nasrollahzadeh, Dariush / Roshandel, Gholamreza / Delhomme, Tiffany Myriam / Avogbe, Patrice Hodonou / Foll, Matthieu / Saidi, Farrokh / Poustchi, Hossein / Sotoudeh, Masoud / Malekzadeh, Reza / Brennan, Paul / Mckay, James / Hainaut, Pierre / Abedi-Ardekani, Behnoush

    International journal of molecular sciences

    2021  Volume 22, Issue 11

    Abstract: Circulating cell-free DNA (cfDNA) is emerging as a potential tumor biomarker. CfDNA-based biomarkers may be applicable in tumors without an available non-invasive screening method among at-risk populations. Esophageal squamous cell carcinoma (ESCC) and ... ...

    Abstract Circulating cell-free DNA (cfDNA) is emerging as a potential tumor biomarker. CfDNA-based biomarkers may be applicable in tumors without an available non-invasive screening method among at-risk populations. Esophageal squamous cell carcinoma (ESCC) and residents of the Asian cancer belt are examples of those malignancies and populations. Previous epidemiological studies using cfDNA have pointed to the need for high volumes of good quality plasma (i.e., >1 mL plasma with 0 or 1 cycles of freeze-thaw) rather than archival serum, which is often the main available source of cfDNA in retrospective studies. Here, we have investigated the concordance of
    MeSH term(s) Circulating Tumor DNA/blood ; Circulating Tumor DNA/genetics ; Esophageal Neoplasms/blood ; Esophageal Neoplasms/genetics ; Esophageal Squamous Cell Carcinoma/blood ; Esophageal Squamous Cell Carcinoma/genetics ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Mutation ; Serum ; Tumor Suppressor Protein p53/blood ; Tumor Suppressor Protein p53/genetics
    Chemical Substances Circulating Tumor DNA ; TP53 protein, human ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2021-05-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22115627
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Genetically Raised Circulating Bilirubin Levels and Risk of Ten Cancers: A Mendelian Randomization Study.

    Seyed Khoei, Nazlisadat / Carreras-Torres, Robert / Murphy, Neil / Gunter, Marc J / Brennan, Paul / Smith-Byrne, Karl / Mariosa, Daniela / Mckay, James / O'Mara, Tracy A / Jarrett, Ruth / Hjalgrim, Henrik / Smedby, Karin E / Cozen, Wendy / Onel, Kenan / Diepstra, Arjan / Wagner, Karl-Heinz / Freisling, Heinz

    Cells

    2021  Volume 10, Issue 2

    Abstract: Bilirubin, an endogenous antioxidant, may play a protective role in cancer development. We applied two-sample Mendelian randomization to investigate whether genetically raised bilirubin levels are causally associated with the risk of ten cancers ( ... ...

    Abstract Bilirubin, an endogenous antioxidant, may play a protective role in cancer development. We applied two-sample Mendelian randomization to investigate whether genetically raised bilirubin levels are causally associated with the risk of ten cancers (pancreas, kidney, endometrium, ovary, breast, prostate, lung, Hodgkin's lymphoma, melanoma, and neuroblastoma). The number of cases and their matched controls of European descent ranged from 122,977 and 105,974 for breast cancer to 1200 and 6417 for Hodgkin's lymphoma, respectively. A total of 115 single-nucleotide polymorphisms (SNPs) associated (
    MeSH term(s) Bilirubin/genetics ; Biomarkers/analysis ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Genome-Wide Association Study ; Humans ; Mendelian Randomization Analysis/methods ; Polymorphism, Single Nucleotide/genetics ; Risk Factors
    Chemical Substances Biomarkers ; Bilirubin (RFM9X3LJ49)
    Language English
    Publishing date 2021-02-15
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10020394
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Clinical characteristics and outcome of 318 families with familial monoclonal gammopathy: A multicenter Intergroupe Francophone du Myélome study.

    Dumontet, Charles / Demangel, Delphine / Galia, Perrine / Karlin, Lionel / Roche, Laurent / Fauvernier, Mathieu / Golfier, Camille / Laude, Marie-Charlotte / Leleu, Xavier / Rodon, Philippe / Roussel, Murielle / Azaïs, Isabelle / Doyen, Chantal / Slama, Borhane / Manier, Salomon / Decaux, Olivier / Pertesi, Maroulio / Beaumont, Marie / Caillot, Denis /
    Boyle, Eileen M / Cliquennois, Manuel / Cony-Makhoul, Pascale / Doncker, Anne-Violaine / Dorvaux, Véronique / Petillon, Marie Odile / Fontan, Jean / Hivert, Bénédicte / Leduc, Isabelle / Leyronnas, Cécile / Macro, Margaret / Maigre, Michel / Mariette, Clara / Mineur, Philippe / Rigaudeau, Sophie / Royer, Bruno / Vincent, Laure / Mckay, James / Perrial, Emeline / Garderet, Laurent

    American journal of hematology

    2023  Volume 98, Issue 2, Page(s) 264–271

    Abstract: Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely ... ...

    Abstract Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely occurs in a familial context. MGUS is observed much more commonly, which can in some cases evolve toward full-blown MM. Although recurrent cytogenetic abnormalities have been described in tumor cells of sporadic cases of MM, the pathogenesis of familial MM remains largely unexplained. In order to identify genetic factors predisposing to familial monoclonal gammopathy, the Intergroupe Francophone du Myélome identified 318 families with at least two confirmed cases of monoclonal gammopathy. There were 169 families with parent/child pairs and 164 families with cases in at least two siblings, compatible with an autosomal transmission. These familial cases were compared with sporadic cases who were matched for age at diagnosis, sex and immunoglobulin isotype, with 10 sporadic cases for each familial case. The gender distribution, age and immunoglobulin subtypes of familial cases were unremarkable in comparison to sporadic cases. With a median follow-up of 7.4 years after diagnosis, the percentage of MGUS cases having evolved to MM was 3%. The median overall survival of the 148 familial MM cases was longer than that of matched sporadic cases, with projected values of 7.6 and 16.1 years in patients older and younger than 65 years, respectively. These data suggest that familial cases of monoclonal gammopathy are similar to sporadic cases in terms of clinical presentation and carry a better prognosis.
    MeSH term(s) Child ; Humans ; Monoclonal Gammopathy of Undetermined Significance/diagnosis ; Paraproteinemias/genetics ; Paraproteinemias/complications ; Multiple Myeloma/pathology ; Prognosis ; Chromosome Aberrations
    Language English
    Publishing date 2023-01-01
    Publishing country United States
    Document type Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 196767-8
    ISSN 1096-8652 ; 0361-8609
    ISSN (online) 1096-8652
    ISSN 0361-8609
    DOI 10.1002/ajh.26785
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: Targeted deep sequencing of plasma circulating cell-free DNA reveals Vimentin and Fibulin 1 as potential epigenetic biomarkers for hepatocellular carcinoma.

    Holmila, Reetta / Sklias, Athena / Muller, David C / Degli Esposti, Davide / Guilloreau, Paule / Mckay, James / Sangrajrang, Suleeporn / Srivatanakul, Petcharin / Hainaut, Pierre / Merle, Philippe / Herceg, Zdenko / Nogueira da Costa, Andre

    PloS one

    2017  Volume 12, Issue 3, Page(s) e0174265

    Abstract: Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, but is still lacking sensitive and specific biomarkers for early diagnosis and prognosis. In this study, we applied targeted massively parallel semiconductor ... ...

    Abstract Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, but is still lacking sensitive and specific biomarkers for early diagnosis and prognosis. In this study, we applied targeted massively parallel semiconductor sequencing to assess methylation on a panel of genes (FBLN1, HINT2, LAMC1, LTBP1, LTBP2, PSMA2, PSMA7, PXDN, TGFB1, UBE2L3, VIM and YWHAZ) in plasma circulating cell-free DNA (cfDNA) and to evaluate the potential of these genes as HCC biomarkers in two different series, one from France (42 HCC cases and 42 controls) and one from Thailand (42 HCC cases, 26 chronic liver disease cases and 42 controls). We also analyzed a set of HCC and adjacent tissues and liver cell lines to further compare with 'The Cancer Genome Atlas' (TCGA) data. The methylation in cfDNA was detected for FBLN1, PSMA7, PXDN and VIM, with differences in methylation patterns between cases and controls for FBLN1 and VIM. The average methylation level across analyzed CpG-sites was associated with higher odds of HCC for VIM (1.48 [1.02, 2.16] for French cases and 2.18 [1.28, 3.72] for Thai cases), and lower odds of HCC for FBLN1 (0.89 [0.76, 1.03] for French cases and 0.75 [0.63, 0.88] for Thai cases). In conclusion, our study provides evidence that changes in VIM and FBLN1 methylation levels in cfDNA are associated with HCC and could represent useful plasma-based biomarkers. Also, the potential to investigate methylation patterns in cfDNA could bring new strategies for HCC detection and monitoring high-risk groups and response to treatment.
    MeSH term(s) Biomarkers/blood ; Calcium-Binding Proteins/genetics ; Carcinoma, Hepatocellular/diagnosis ; Carcinoma, Hepatocellular/genetics ; DNA/blood ; DNA/genetics ; DNA Methylation ; Epigenomics/methods ; Genetic Markers/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Liver Neoplasms/diagnosis ; Liver Neoplasms/genetics ; Prognosis ; Vimentin/genetics
    Chemical Substances Biomarkers ; Calcium-Binding Proteins ; Genetic Markers ; Vimentin ; fibulin ; DNA (9007-49-2)
    Language English
    Publishing date 2017-03-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0174265
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top