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Expression of HK2, PKM2, and PFKM Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients

The reprogramming of energy metabolism is one of the hallmarks of cancer and is crucial for tumor progression. Altered aerobic glycolysis is a well-known characteristic of cancer cell metabolism. In the present study, the expression profiles of key metabolic genes (HK2, PFKM, and PKM2) were assessed...

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Autores principales: Ishfaq, Mehreen, Bashir, Nabiha, Riaz, Syeda Kiran, Manzoor, Shumaila, Khan, Jahangir Sarwar, Bibi, Yamin, Sami, Rokayya, Aljahani, Amani H., Alharthy, Saif A., Shahid, Ramla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955648/
https://www.ncbi.nlm.nih.gov/pubmed/35328104
http://dx.doi.org/10.3390/genes13030549
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author Ishfaq, Mehreen
Bashir, Nabiha
Riaz, Syeda Kiran
Manzoor, Shumaila
Khan, Jahangir Sarwar
Bibi, Yamin
Sami, Rokayya
Aljahani, Amani H.
Alharthy, Saif A.
Shahid, Ramla
author_facet Ishfaq, Mehreen
Bashir, Nabiha
Riaz, Syeda Kiran
Manzoor, Shumaila
Khan, Jahangir Sarwar
Bibi, Yamin
Sami, Rokayya
Aljahani, Amani H.
Alharthy, Saif A.
Shahid, Ramla
author_sort Ishfaq, Mehreen
collection PubMed
description The reprogramming of energy metabolism is one of the hallmarks of cancer and is crucial for tumor progression. Altered aerobic glycolysis is a well-known characteristic of cancer cell metabolism. In the present study, the expression profiles of key metabolic genes (HK2, PFKM, and PKM2) were assessed in the breast cancer cohort of Pakistan using quantitative polymerase chain reaction (qPCR) and IHC. Expression patterns were correlated with molecular subtypes and clinical parameters in the patients. A significant upregulation of key glycolytic genes was observed in tumor samples in comparison to their adjacent controls (p < 0.0001). The expression of the studied glycolytic genes was significantly increased in late clinical stages, positive nodal involvement, and distant metastasis (p < 0.05). HK2 and PKM2 were found to be upregulated in luminal B, whereas PFKM was overexpressed in the luminal A subtype of breast cancer. The genes were positively correlated with the proliferation marker Ki67 (p < 0.001). Moreover, moderate positive linear correlations between HK2 and PKM2 (r = 0.476), HK2 and PFKM (r = 0.473), and PKM2 and PFKM (r = 0.501) were also observed (p < 0.01). These findings validate that the key regulatory genes in glycolysis can serve as potential biomarkers and/or molecular targets for breast cancer management. However, the clinical significance of these molecules needs to be further validated through in vitro and in vivo experiments.
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spelling pubmed-89556482022-03-26 Expression of HK2, PKM2, and PFKM Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients Ishfaq, Mehreen Bashir, Nabiha Riaz, Syeda Kiran Manzoor, Shumaila Khan, Jahangir Sarwar Bibi, Yamin Sami, Rokayya Aljahani, Amani H. Alharthy, Saif A. Shahid, Ramla Genes (Basel) Article The reprogramming of energy metabolism is one of the hallmarks of cancer and is crucial for tumor progression. Altered aerobic glycolysis is a well-known characteristic of cancer cell metabolism. In the present study, the expression profiles of key metabolic genes (HK2, PFKM, and PKM2) were assessed in the breast cancer cohort of Pakistan using quantitative polymerase chain reaction (qPCR) and IHC. Expression patterns were correlated with molecular subtypes and clinical parameters in the patients. A significant upregulation of key glycolytic genes was observed in tumor samples in comparison to their adjacent controls (p < 0.0001). The expression of the studied glycolytic genes was significantly increased in late clinical stages, positive nodal involvement, and distant metastasis (p < 0.05). HK2 and PKM2 were found to be upregulated in luminal B, whereas PFKM was overexpressed in the luminal A subtype of breast cancer. The genes were positively correlated with the proliferation marker Ki67 (p < 0.001). Moreover, moderate positive linear correlations between HK2 and PKM2 (r = 0.476), HK2 and PFKM (r = 0.473), and PKM2 and PFKM (r = 0.501) were also observed (p < 0.01). These findings validate that the key regulatory genes in glycolysis can serve as potential biomarkers and/or molecular targets for breast cancer management. However, the clinical significance of these molecules needs to be further validated through in vitro and in vivo experiments. MDPI 2022-03-20 /pmc/articles/PMC8955648/ /pubmed/35328104 http://dx.doi.org/10.3390/genes13030549 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
Ishfaq, Mehreen
Bashir, Nabiha
Riaz, Syeda Kiran
Manzoor, Shumaila
Khan, Jahangir Sarwar
Bibi, Yamin
Sami, Rokayya
Aljahani, Amani H.
Alharthy, Saif A.
Shahid, Ramla
Expression of HK2, PKM2, and PFKM Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients
title Expression of HK2, PKM2, and PFKM Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients
title_full Expression of HK2, PKM2, and PFKM Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients
title_fullStr Expression of HK2, PKM2, and PFKM Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients
title_full_unstemmed Expression of HK2, PKM2, and PFKM Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients
title_short Expression of HK2, PKM2, and PFKM Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients
title_sort expression of hk2, pkm2, and pfkm is associated with metastasis and late disease onset in breast cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955648/
https://www.ncbi.nlm.nih.gov/pubmed/35328104
http://dx.doi.org/10.3390/genes13030549
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