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Functional genomic mRNA profiling of a large cancer data base demonstrates mesothelin overexpression in a broad range of tumor types.

ABSTRACT: The membrane bound glycoprotein mesothelin (MSLN) is a highly specific tumor marker, which is currently exploited as target for drugs. There are only limited data available on MSLN expression by human tumors. Therefore we determined overexpression of MSLN across different tumor types with Functional Genomic mRNA (FGM) profiling of a large cancer database. Results were compared with data in articles reporting immunohistochemical (IHC) MSLN tumor expression. FGM profiling is a technique that allows prediction of biologically relevant overexpression of proteins from a robust data set of mRNA microarrays. This technique was used in a database comprising 19,746 tumors to identify for 41 tumor types the percentage of samples with an overexpression of MSLN compared to a normal background. A literature search was performed to compare the FGM profiling data with studies reporting IHC MSLN tumor expression. FGM profiling showed MSLN overexpression in gastrointestinal (12-36%) and gynecological tumors (20-66%), non-small cell lung cancer (21%) and synovial sarcomas (30%). The overexpression found in thyroid cancers (5%) and renal cell cancers (10%) was not yet reported with IHC analyses. We observed that MSLN amplification rate within esophageal cancer depends on the histotype (31% for adenocarcinomas versus 3% for squamous-cell carcinomas). Subset analysis in breast cancer showed MSLN amplification rates of 28% in triple-negative breast cancer (TNBC) and 33% in basal-like breast cancer. Further subtype analysis of TNBCs showed the highest amplification rate (42%) in the basal-like 1 subtype and the lowest amplification rate (9%) in the luminal androgen receptor subtype.

SUBMITTER: Lamberts LE

PROVIDER: S-EPMC4695051 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Functional genomic mRNA profiling of a large cancer data base demonstrates mesothelin overexpression in a broad range of tumor types.

Lamberts Laetitia E LE de Groot Derk Jan A DJ Bense Rico D RD de Vries Elisabeth G E EG Fehrmann Rudolf S N RS

Oncotarget 20150901 29

The membrane bound glycoprotein mesothelin (MSLN) is a highly specific tumor marker, which is currently exploited as target for drugs. There are only limited data available on MSLN expression by human tumors. Therefore we determined overexpression of MSLN across different tumor types with Functional Genomic mRNA (FGM) profiling of a large cancer database. Results were compared with data in articles reporting immunohistochemical (IHC) MSLN tumor expression. FGM profiling is a technique that allow ...[more]

PMID: 26172299

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Project description:Attack by herbivores is a major biotic stress limiting the soybean crop production. Plant defenses against caterpillars include the production of secondary metabolites such as flavonoids, which constitute a diverse group of plant secondary metabolites. Thus, a more discriminate metabolic profiling between genotypes are important for a more comprehensive and reliable characterization of soybean resistance. Therefore, in this study a non-targeted LC/MS-based for analysis of flavonoid profiles of soybean genotypes contrasting to the resistance to A. gemmatalis was applied. Clustering analysis revealed profiles highly distinct between the susceptible UFV 105 AP and the resistant IAC 17 genotypes. This comparative approach enables to identify directly from leaf extract some new compounds related to resistance, some of which were present in higher abundance specifically in the IAC 17 genotype: four Quercetin conjugates, Rutin (Quercetin 3-O-Rutinoside), Quercetin-3,7-O- di-glucoside, Quercetin-3-O-rhamnosylglycoside-7-O-glucoside and Quercetin-3-O-rhamnopyranosyl-glucopyranoside-rhamnopyranoside; two Genistein conjugates, Genistein-7-O-diglucoside-dimalonylated and Genistein-7-O-6-O-malonylglucoside; and one Daidzein conjugate, Daidzein-7-O-Glucoside-malonate. The most abundant flavonoid glycoconjugates in soybean leaves belongs to Quercetin and Kaempferol classes. However, only one from the identified compounds was classified as a Kaempferol. The Kaempferol-3-O-L-rhamnopyranosyl-glucopyranoside showed high abundance in the resistant genotype IAC 17. The metabolic profiles generated by LC/MS allowed the reconstruction of the flavonoid biosynthetic pathways, which revealed a constitutive character for herbivory resistance in the resistant genotype IAC-17 and a metabolic regulation for the rechanneling of Quercetin, Kaempferol and Genistein conjugates in soybean. Highest relative abundances were detected for glyconjugates, such as Rutin, Quercetin 3-O-rhamnosylglycoside-7-O-glucoside and Quercitin-3-O-rhamnopyranosyl-glucopyranoside-rhamnopyranoside in the leaves of the resistant genotype.

Dataset Information

Functional genomic mRNA profiling of a large cancer data base demonstrates mesothelin overexpression in a broad range of tumor types.

Publications

Functional genomic mRNA profiling of a large cancer data base demonstrates mesothelin overexpression in a broad range of tumor types.

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