Expression of <i>HK2, PKM2,</i> and <i>PFKM</i> 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 (<i>HK2</i>, <i>P...
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MDPI AG
2022-03-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/3/549 |
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| author | Mehreen Ishfaq Nabiha Bashir Syeda Kiran Riaz Shumaila Manzoor Jahangir Sarwar Khan Yamin Bibi Rokayya Sami Amani H. Aljahani Saif A. Alharthy Ramla Shahid |
| author_facet | Mehreen Ishfaq Nabiha Bashir Syeda Kiran Riaz Shumaila Manzoor Jahangir Sarwar Khan Yamin Bibi Rokayya Sami Amani H. Aljahani Saif A. Alharthy Ramla Shahid |
| author_sort | Mehreen Ishfaq |
| collection | DOAJ |
| 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 (<i>HK2</i>, <i>PFKM,</i> and <i>PKM2</i>) 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 (<i>p</i> < 0.0001). The expression of the studied glycolytic genes was significantly increased in late clinical stages, positive nodal involvement, and distant metastasis (<i>p</i> < 0.05). <i>HK2</i> and <i>PKM2</i> were found to be upregulated in luminal B, whereas <i>PFKM</i> was overexpressed in the luminal A subtype of breast cancer. The genes were positively correlated with the proliferation marker <i>Ki67</i> (<i>p</i> < 0.001). Moreover, moderate positive linear correlations between <i>HK2</i> and <i>PKM2</i> (r = 0.476), <i>HK2</i> and <i>PFKM</i> (r = 0.473), and <i>PKM2</i> and <i>PFKM</i> (r = 0.501) were also observed (<i>p</i> < 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. |
| first_indexed | 2024-03-09T19:47:12Z |
| format | Article |
| id | doaj.art-567e8565755b4758a27088c214963720 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T19:47:12Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-567e8565755b4758a27088c2149637202023-11-24T01:20:00ZengMDPI AGGenes2073-44252022-03-0113354910.3390/genes13030549Expression of <i>HK2, PKM2,</i> and <i>PFKM</i> Is Associated with Metastasis and Late Disease Onset in Breast Cancer PatientsMehreen Ishfaq0Nabiha Bashir1Syeda Kiran Riaz2Shumaila Manzoor3Jahangir Sarwar Khan4Yamin Bibi5Rokayya Sami6Amani H. Aljahani7Saif A. Alharthy8Ramla Shahid9Department of Biosciences, COMSATS University Islamabad, Islamabad 44000, PakistanDepartment of Biosciences, COMSATS University Islamabad, Islamabad 44000, PakistanDepartment of Molecular Biology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, PakistanNational Veterinary Lab, National Agricultural Research Centre, Islamabad 44000, PakistanDepartment of General Surgery, Rawalpindi Medical University, Rawalpindi 46000, PakistanDepartment of Botany, PMAS-Arid Agriculture University Rawalpindi, Rawalpindi 46300, PakistanDepartment of Food Science and Nutrition, College of Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaDepartment of Physical Sport Science, College of Education, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi ArabiaDepartment of Biosciences, COMSATS University Islamabad, Islamabad 44000, PakistanThe 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 (<i>HK2</i>, <i>PFKM,</i> and <i>PKM2</i>) 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 (<i>p</i> < 0.0001). The expression of the studied glycolytic genes was significantly increased in late clinical stages, positive nodal involvement, and distant metastasis (<i>p</i> < 0.05). <i>HK2</i> and <i>PKM2</i> were found to be upregulated in luminal B, whereas <i>PFKM</i> was overexpressed in the luminal A subtype of breast cancer. The genes were positively correlated with the proliferation marker <i>Ki67</i> (<i>p</i> < 0.001). Moreover, moderate positive linear correlations between <i>HK2</i> and <i>PKM2</i> (r = 0.476), <i>HK2</i> and <i>PFKM</i> (r = 0.473), and <i>PKM2</i> and <i>PFKM</i> (r = 0.501) were also observed (<i>p</i> < 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.https://www.mdpi.com/2073-4425/13/3/549aerobic glycolysisbreast cancer<i>HK2</i><i>PFKM</i><i>PKM2</i>Warburg effect |
| spellingShingle | Mehreen Ishfaq Nabiha Bashir Syeda Kiran Riaz Shumaila Manzoor Jahangir Sarwar Khan Yamin Bibi Rokayya Sami Amani H. Aljahani Saif A. Alharthy Ramla Shahid Expression of <i>HK2, PKM2,</i> and <i>PFKM</i> Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients Genes aerobic glycolysis breast cancer <i>HK2</i> <i>PFKM</i> <i>PKM2</i> Warburg effect |
| title | Expression of <i>HK2, PKM2,</i> and <i>PFKM</i> Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients |
| title_full | Expression of <i>HK2, PKM2,</i> and <i>PFKM</i> Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients |
| title_fullStr | Expression of <i>HK2, PKM2,</i> and <i>PFKM</i> Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients |
| title_full_unstemmed | Expression of <i>HK2, PKM2,</i> and <i>PFKM</i> Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients |
| title_short | Expression of <i>HK2, PKM2,</i> and <i>PFKM</i> Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients |
| title_sort | expression of i hk2 pkm2 i and i pfkm i is associated with metastasis and late disease onset in breast cancer patients |
| topic | aerobic glycolysis breast cancer <i>HK2</i> <i>PFKM</i> <i>PKM2</i> Warburg effect |
| url | https://www.mdpi.com/2073-4425/13/3/549 |
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