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Energy Substrate Transporters in High-Grade Ovarian Cancer: Gene Expression and Clinical Implications
Ovarian cancer is a non-homogenous malignancy. High-grade serous carcinoma (HGSC) is the most common subtype, and its drug resistance mechanisms remain unclear. Despite the advantages of modern pharmacotherapy, high-grade ovarian cancer is associated with a poor prognosis and research into targeted...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408757/ https://www.ncbi.nlm.nih.gov/pubmed/36012230 http://dx.doi.org/10.3390/ijms23168968 |
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author | Baczewska, Marta Supruniuk, Elżbieta Bojczuk, Klaudia Guzik, Paweł Milewska, Patrycja Konończuk, Katarzyna Dobroch, Jakub Chabowski, Adrian Knapp, Paweł |
author_facet | Baczewska, Marta Supruniuk, Elżbieta Bojczuk, Klaudia Guzik, Paweł Milewska, Patrycja Konończuk, Katarzyna Dobroch, Jakub Chabowski, Adrian Knapp, Paweł |
author_sort | Baczewska, Marta |
collection | PubMed |
description | Ovarian cancer is a non-homogenous malignancy. High-grade serous carcinoma (HGSC) is the most common subtype, and its drug resistance mechanisms remain unclear. Despite the advantages of modern pharmacotherapy, high-grade ovarian cancer is associated with a poor prognosis and research into targeted therapies is in progress. The aim of the study was to assess the dominant energy substrate transport mechanism in ovarian cancer cells and to verify whether genomic aberrations could predict clinical outcomes using the Cancer Genome Atlas (TCGA) dataset. Total RNA was extracted from HGSC frozen tissues, and the expression of selected genes was compared to respective controls. GLUT1, FABPpm, MCT4 and SNAT1 genes were significantly overexpressed in carcinomas compared with controls, while expression of CD36/SR-B2, FATP1, FABP4, GLUT4, ASCT2 and LPL was decreased. No differences were found in FATP4, LAT1, MCT1 and FASN. The transcript content of mitochondrial genes such as PGC-1α, TFAM and COX4/1 was similar between groups, while the β-HAD level declined in ovarian cancer. Additionally, the MCT4 level was reduced and PGC-1α was elevated in cancer tissue from patients with ‘small’ primary tumor and omental invasion accompanied by ascites as compared to patients that exhibited greater tendencies to metastasize to lymph nodes with clear omentum. Based on TCGA, higher FABP4 and LPL and lower TFAM expression indicated poorer overall survival in patients with ovarian cancer. In conclusion, the presented data show that there is no exclusive energy substrate in HGSC. However, this study indicates the advantage of glucose and lactate transport over fatty acids, thereby suggesting potential therapeutic intervention targets to impede ovarian cancer growth. |
format | Online Article Text |
id | pubmed-9408757 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94087572022-08-26 Energy Substrate Transporters in High-Grade Ovarian Cancer: Gene Expression and Clinical Implications Baczewska, Marta Supruniuk, Elżbieta Bojczuk, Klaudia Guzik, Paweł Milewska, Patrycja Konończuk, Katarzyna Dobroch, Jakub Chabowski, Adrian Knapp, Paweł Int J Mol Sci Article Ovarian cancer is a non-homogenous malignancy. High-grade serous carcinoma (HGSC) is the most common subtype, and its drug resistance mechanisms remain unclear. Despite the advantages of modern pharmacotherapy, high-grade ovarian cancer is associated with a poor prognosis and research into targeted therapies is in progress. The aim of the study was to assess the dominant energy substrate transport mechanism in ovarian cancer cells and to verify whether genomic aberrations could predict clinical outcomes using the Cancer Genome Atlas (TCGA) dataset. Total RNA was extracted from HGSC frozen tissues, and the expression of selected genes was compared to respective controls. GLUT1, FABPpm, MCT4 and SNAT1 genes were significantly overexpressed in carcinomas compared with controls, while expression of CD36/SR-B2, FATP1, FABP4, GLUT4, ASCT2 and LPL was decreased. No differences were found in FATP4, LAT1, MCT1 and FASN. The transcript content of mitochondrial genes such as PGC-1α, TFAM and COX4/1 was similar between groups, while the β-HAD level declined in ovarian cancer. Additionally, the MCT4 level was reduced and PGC-1α was elevated in cancer tissue from patients with ‘small’ primary tumor and omental invasion accompanied by ascites as compared to patients that exhibited greater tendencies to metastasize to lymph nodes with clear omentum. Based on TCGA, higher FABP4 and LPL and lower TFAM expression indicated poorer overall survival in patients with ovarian cancer. In conclusion, the presented data show that there is no exclusive energy substrate in HGSC. However, this study indicates the advantage of glucose and lactate transport over fatty acids, thereby suggesting potential therapeutic intervention targets to impede ovarian cancer growth. MDPI 2022-08-11 /pmc/articles/PMC9408757/ /pubmed/36012230 http://dx.doi.org/10.3390/ijms23168968 Text en © 2022 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 Baczewska, Marta Supruniuk, Elżbieta Bojczuk, Klaudia Guzik, Paweł Milewska, Patrycja Konończuk, Katarzyna Dobroch, Jakub Chabowski, Adrian Knapp, Paweł Energy Substrate Transporters in High-Grade Ovarian Cancer: Gene Expression and Clinical Implications |
title | Energy Substrate Transporters in High-Grade Ovarian Cancer: Gene Expression and Clinical Implications |
title_full | Energy Substrate Transporters in High-Grade Ovarian Cancer: Gene Expression and Clinical Implications |
title_fullStr | Energy Substrate Transporters in High-Grade Ovarian Cancer: Gene Expression and Clinical Implications |
title_full_unstemmed | Energy Substrate Transporters in High-Grade Ovarian Cancer: Gene Expression and Clinical Implications |
title_short | Energy Substrate Transporters in High-Grade Ovarian Cancer: Gene Expression and Clinical Implications |
title_sort | energy substrate transporters in high-grade ovarian cancer: gene expression and clinical implications |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408757/ https://www.ncbi.nlm.nih.gov/pubmed/36012230 http://dx.doi.org/10.3390/ijms23168968 |
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