Dataset Information

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 | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Bååth Maria M Jönsson Jenny-Maria JM Westbom Fremer Sofia S Martín de la Fuente Laura L Tran Lena L Malander Susanne S Kannisto Päivi P Måsbäck Anna A Honeth Gabriella G Hedenfalk Ingrid I

Genes 20210514 5

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 wi ...[more]

PMID: 34069138

Similar Datasets

Project description:BackgroundA validated prognostic index for the outcome of patients with advanced high-grade serous ovarian cancer (HGSOC) undergoing neoadjuvant chemotherapy (NACT) remains elusive. To address this need, we developed an ovarian neoadjuvant chemotherapy prognostic index (ONCPI) to improve predictive accuracy.MethodsWe encompassed an analysis of the clinicopathological characteristics of patients with advanced HGSOC who were administered platinum-based NACT. Blood inflammatory composite markers were calculated and converted into binary values using optimal cutoffs. Omental hematoxylin and eosin (H&E) stained slides were selected for the assessment of chemotherapy response score (CRS), which served as a measure of NACT efficacy. Logistic regression analysis and Cox proportional hazards regression model were utilized to construct a prognostic index.ResultsMultivariate logistic analysis showed that both CRS and neutrophil-to-lymphocyte ratio (NLR) independently influenced the response to platinum-based chemotherapy. Meanwhile, Kaplan-Meier and Cox regression analysis revealed that CRS score was significantly correlated with progression-free survival (PFS) and overall survival (OS), and patients with high NLR showed poor OS. We further developed an ovarian neoadjuvant chemotherapy prognostic index (ONCPI) based on the CRS and NLR. The area under the curve (AUC) value of ONCPI was 0.771 (P < 0.001, 95% CI: 0.656-0.887) for the prediction of platinum resistance. This AUC value surpasses that of the individual NLR and CRS, which were 0.670 (P = 0.018, 95% CI: 0.547-0.793) and 0.714 (P = 0.003, 95% CI: 0.590-0.839), respectively. Moreover, survival analysis suggested that patients with ONCPI of 0 and 1 were significantly associated with improved PFS and OS.ConclusionsThe ONCPI emerges as a significant prognostic marker for predicting NACT outcome in advanced HGSOC patients and holds promise for integration into clinical practice and risk-stratified trial design.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets