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MET Expression and Cancer Stem Cell Networks Impact Outcome in High-Grade Serous Ovarian Cancer.

ABSTRACT: Overexpression of the receptor tyrosine kinase MET has been linked to poor survival in several cancer types, and MET has been suggested to interact with stem cell networks. In vitro studies have further suggested a possible benefit of a combined treatment using PARP and MET inhibitors. We used a tissue microarray (TMA) with 130 samples of advanced-stage high-grade serous fallopian tube/ovarian cancer (HGSC) to investigate the prognostic value of MET protein expression alone and in combination with the stem cell factor SOX2. The possible synergistic effects of a PARP and MET inhibitor treatment were evaluated in two cell lines with BRCA1 or BRCA2 deficiency and in their BRCA1/2-proficient counterparts. Patients with tumors positive for MET had worse overall survival (log-rank test, p = 0.015) compared to patients with MET-negative tumors. The prognostic role of MET was even more prominent in the subgroup of patients with SOX2-negative tumors (p = 0.0081). No synergistic effects of the combined treatment with PARP and MET inhibitors were found in the cell lines examined. We conclude that MET expression could be used as a marker for OS in HGSC and that stemness should be taken into consideration when evaluating the mechanisms of this effect.

SUBMITTER: Baath M

PROVIDER: S-EPMC8155853 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Profiles of genomic instability in high-grade serous ovarian cancer predict treatment outcome.

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ZIP4 Is a Novel Cancer Stem Cell Marker in High-Grade Serous Ovarian Cancer.

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Effect of BRCA mutational status on survival outcome in advanced-stage high-grade serous ovarian cancer.

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| S-EPMC4055662 | biostudies-literature

Profiles of genomic instability in high-grade serous ovarian cancer (HGSC) predict treatment outcome

Project description:Profiling of loss of heterozygosity (LOH) in HGSC, subcrouping HGSC by LOH-based clustering and comparing to the LOH profiles of triple-negative breast cancer [previously submitted; GSE19594]. Study for the correlation of LOH burdern and LOH-based subgroups to clinical response to platinum-based chemotherapy in patients suffered from HGSC. SNP data (Affymetrix GenChip 250K SNP Nsp) from 47 high grade serous ovarian cancer were generated and used for LOH and copy number analysis, LOH-based hierarchical clustering to subclassify HGSC, and comparison to the chromosomal alterations in high grade brest cancer. The associstion between LOH-based subgroups and LOH burden and clinical resposne to platinum-based chemotherapy was investigated. The results were validated in two independent public opening datasets.

2012-11-06 | E-GEOD-39130 | biostudies-arrayexpress

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