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Cancer Stem Cell Markers—Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis

Cancer stem cells (CSCs) may contribute to an increased risk of recurrence in ovarian cancer (OC). Further research is needed to identify associations between CSC markers and OC patients’ clinical outcomes with greater certainty. If they prove to be correct, in the future, the CSC markers can be use...

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Autores principales: Iżycka, Natalia, Zaborowski, Mikołaj Piotr, Ciecierski, Łukasz, Jaz, Kamila, Szubert, Sebastian, Miedziarek, Cezary, Rezler, Marta, Piątek-Bajan, Kinga, Synakiewicz, Aneta, Jankowska, Anna, Figlerowicz, Marek, Sterzyńska, Karolina, Nowak-Markwitz, Ewa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454196/
https://www.ncbi.nlm.nih.gov/pubmed/37628927
http://dx.doi.org/10.3390/ijms241612746
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author Iżycka, Natalia
Zaborowski, Mikołaj Piotr
Ciecierski, Łukasz
Jaz, Kamila
Szubert, Sebastian
Miedziarek, Cezary
Rezler, Marta
Piątek-Bajan, Kinga
Synakiewicz, Aneta
Jankowska, Anna
Figlerowicz, Marek
Sterzyńska, Karolina
Nowak-Markwitz, Ewa
author_facet Iżycka, Natalia
Zaborowski, Mikołaj Piotr
Ciecierski, Łukasz
Jaz, Kamila
Szubert, Sebastian
Miedziarek, Cezary
Rezler, Marta
Piątek-Bajan, Kinga
Synakiewicz, Aneta
Jankowska, Anna
Figlerowicz, Marek
Sterzyńska, Karolina
Nowak-Markwitz, Ewa
author_sort Iżycka, Natalia
collection PubMed
description Cancer stem cells (CSCs) may contribute to an increased risk of recurrence in ovarian cancer (OC). Further research is needed to identify associations between CSC markers and OC patients’ clinical outcomes with greater certainty. If they prove to be correct, in the future, the CSC markers can be used to help predict survival and indicate new therapeutic targets. This study aimed to determine the CSC markers at mRNA and protein levels and their association with clinical presentation, outcome, and risk of recurrence in HGSOC (High-Grade Serous Ovarian Cancer). TCGA (The Cancer Genome Atlas) database with 558 ovarian cancer tumor samples was used for the evaluation of 13 CSC markers (ALDH1A1, CD44, EPCAM, KIT, LGR5, NES, NOTCH3, POU5F1, PROM1, PTTG1, ROR1, SOX9, and THY1). Data on mRNA and protein levels assessed by microarray and mass spectrometry were retrieved from TCGA. Models to predict chemotherapy response and survival were built using multiple variables, including epidemiological data, expression levels, and machine learning methodology. ALDH1A1 and LGR5 mRNA expressions indicated a higher platinum sensitivity (p = 3.50 × 10(−3); p = 0.01, respectively). POU5F1 mRNA expression marked platinum-resistant tumors (p = 9.43 × 10(−3)). CD44 and EPCAM mRNA expression correlated with longer overall survival (OS) (p = 0.043; p = 0.039, respectively). THY1 mRNA and protein levels were associated with worse OS (p = 0.019; p = 0.015, respectively). Disease-free survival (DFS) was positively affected by EPCAM (p = 0.004), LGR5 (p = 0.018), and CD44 (p = 0.012). In the multivariate model based on CSC marker expression, the high-risk group had 9.1 months longer median overall survival than the low-risk group (p < 0.001). ALDH1A1, CD44, EPCAM, LGR5, POU5F1, and THY1 levels in OC may be used as prognostic factors for the primary outcome and help predict the treatment response.
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spelling pubmed-104541962023-08-26 Cancer Stem Cell Markers—Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis Iżycka, Natalia Zaborowski, Mikołaj Piotr Ciecierski, Łukasz Jaz, Kamila Szubert, Sebastian Miedziarek, Cezary Rezler, Marta Piątek-Bajan, Kinga Synakiewicz, Aneta Jankowska, Anna Figlerowicz, Marek Sterzyńska, Karolina Nowak-Markwitz, Ewa Int J Mol Sci Article Cancer stem cells (CSCs) may contribute to an increased risk of recurrence in ovarian cancer (OC). Further research is needed to identify associations between CSC markers and OC patients’ clinical outcomes with greater certainty. If they prove to be correct, in the future, the CSC markers can be used to help predict survival and indicate new therapeutic targets. This study aimed to determine the CSC markers at mRNA and protein levels and their association with clinical presentation, outcome, and risk of recurrence in HGSOC (High-Grade Serous Ovarian Cancer). TCGA (The Cancer Genome Atlas) database with 558 ovarian cancer tumor samples was used for the evaluation of 13 CSC markers (ALDH1A1, CD44, EPCAM, KIT, LGR5, NES, NOTCH3, POU5F1, PROM1, PTTG1, ROR1, SOX9, and THY1). Data on mRNA and protein levels assessed by microarray and mass spectrometry were retrieved from TCGA. Models to predict chemotherapy response and survival were built using multiple variables, including epidemiological data, expression levels, and machine learning methodology. ALDH1A1 and LGR5 mRNA expressions indicated a higher platinum sensitivity (p = 3.50 × 10(−3); p = 0.01, respectively). POU5F1 mRNA expression marked platinum-resistant tumors (p = 9.43 × 10(−3)). CD44 and EPCAM mRNA expression correlated with longer overall survival (OS) (p = 0.043; p = 0.039, respectively). THY1 mRNA and protein levels were associated with worse OS (p = 0.019; p = 0.015, respectively). Disease-free survival (DFS) was positively affected by EPCAM (p = 0.004), LGR5 (p = 0.018), and CD44 (p = 0.012). In the multivariate model based on CSC marker expression, the high-risk group had 9.1 months longer median overall survival than the low-risk group (p < 0.001). ALDH1A1, CD44, EPCAM, LGR5, POU5F1, and THY1 levels in OC may be used as prognostic factors for the primary outcome and help predict the treatment response. MDPI 2023-08-13 /pmc/articles/PMC10454196/ /pubmed/37628927 http://dx.doi.org/10.3390/ijms241612746 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Iżycka, Natalia
Zaborowski, Mikołaj Piotr
Ciecierski, Łukasz
Jaz, Kamila
Szubert, Sebastian
Miedziarek, Cezary
Rezler, Marta
Piątek-Bajan, Kinga
Synakiewicz, Aneta
Jankowska, Anna
Figlerowicz, Marek
Sterzyńska, Karolina
Nowak-Markwitz, Ewa
Cancer Stem Cell Markers—Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis
title Cancer Stem Cell Markers—Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis
title_full Cancer Stem Cell Markers—Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis
title_fullStr Cancer Stem Cell Markers—Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis
title_full_unstemmed Cancer Stem Cell Markers—Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis
title_short Cancer Stem Cell Markers—Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis
title_sort cancer stem cell markers—clinical relevance and prognostic value in high-grade serous ovarian cancer (hgsoc) based on the cancer genome atlas analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454196/
https://www.ncbi.nlm.nih.gov/pubmed/37628927
http://dx.doi.org/10.3390/ijms241612746
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