Expression of HIF-1α and markers of angiogenesis and metabolic adaptation in molecular subtypes of breast cancer
Abstract Hypoxic zones exist in solid tumors, where oxygen levels are significantly lower than in normal tissues. Hypoxia makes chemo-radiation therapeutics less effective and renders the metastatic potential more favorable. Emerging research has found that the transcriptional expression of hypoxia-...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Translational Medicine Communications |
| Online Access: | https://doi.org/10.1186/s41231-023-00135-x |
| _version_ | 1811175765276884992 |
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| author | Muzamil Farooq Gh. Rasool Bhat Syed Besina Natasha Thakur Sheikh Zahoor Rafiq A. Rather Ifra Mushtaq Sadaf Dar Bilal Rah Ajaz A. Bhat Muzafar A. Macha Dil Afroze |
| author_facet | Muzamil Farooq Gh. Rasool Bhat Syed Besina Natasha Thakur Sheikh Zahoor Rafiq A. Rather Ifra Mushtaq Sadaf Dar Bilal Rah Ajaz A. Bhat Muzafar A. Macha Dil Afroze |
| author_sort | Muzamil Farooq |
| collection | DOAJ |
| description | Abstract Hypoxic zones exist in solid tumors, where oxygen levels are significantly lower than in normal tissues. Hypoxia makes chemo-radiation therapeutics less effective and renders the metastatic potential more favorable. Emerging research has found that the transcriptional expression of hypoxia-inducible factor-1alpha (HIF-1α) promotes the transcription of vascular endothelial growth factor A (VEGF-A) and Hexokinase-I (HK-I), which are associated to cellular growth, angiogenesis, and metastatic invasion in many malignancies. However, it is still unclear whether VEGFA and HK-I expression has any influence on survival based on the intrinsic subtypes of breast cancer. Their prognostic significance remains a debatable topic. In the present study, quantitative Real-time polymerase chain reaction (qRT-PCR) was employed to check the relative expression of HIF-1α, VEGF-A and HK-I. The hazard ratios (HR) of breast cancer-specific and overall mortality were calculated using Cox proportional hazards model, which were adjusted for demographic, clinicopathological, and associated molecular variables, as well as the diagnosis year. The relative mRNA expression levels of HIF-1α (p = 0.0010) and VEGFA (p = 0.0119) were significantly higher in tumor tissues. The expression of both HIF-1α (p = 0.0111) and VEGFA (p = 0.0078) was higher in the TNBC group of breast cancers, while HK-I (p = 0.0106) was higher in ER/PR-positive, HER2-negative group. HIF-1α and HK-I overexpression were associated with a higher likelihood of survival, while overexpression of VEGFA was associated with a low survival rate, although it was not statistically significant. |
| first_indexed | 2024-04-10T19:42:16Z |
| format | Article |
| id | doaj.art-a96a3fe06d42481dae75059344b8d367 |
| institution | Directory Open Access Journal |
| issn | 2396-832X |
| language | English |
| last_indexed | 2024-04-10T19:42:16Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Medicine Communications |
| spelling | doaj.art-a96a3fe06d42481dae75059344b8d3672023-01-29T12:17:30ZengBMCTranslational Medicine Communications2396-832X2023-01-018111310.1186/s41231-023-00135-xExpression of HIF-1α and markers of angiogenesis and metabolic adaptation in molecular subtypes of breast cancerMuzamil Farooq0Gh. Rasool Bhat1Syed Besina2Natasha Thakur3Sheikh Zahoor4Rafiq A. Rather5Ifra Mushtaq6Sadaf Dar7Bilal Rah8Ajaz A. Bhat9Muzafar A. Macha10Dil Afroze11Advanced Centre for Human Genetics, Sher-I- Kashmir Institute of Medical SciencesAdvanced Centre for Human Genetics, Sher-I- Kashmir Institute of Medical SciencesDepartment of Pathology, Sher-I- Kashmir Institute of Medical SciencesDepartment of General Surgery, Sher-I- Kashmir Institute of Medical SciencesDepartment of Surgical Oncology, Sher-I- Kashmir Institute of Medical SciencesAdvanced Centre for Human Genetics, Sher-I- Kashmir Institute of Medical SciencesAdvanced Centre for Human Genetics, Sher-I- Kashmir Institute of Medical SciencesAdvanced Centre for Human Genetics, Sher-I- Kashmir Institute of Medical SciencesIron Biology Group, Research Institute of Medical & Health Sciences, University of SharjahDepartment of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra MedicineWatson-Crick Centre for Molecular Medicine, Islamic University of Science and TechnologyAdvanced Centre for Human Genetics, Sher-I- Kashmir Institute of Medical SciencesAbstract Hypoxic zones exist in solid tumors, where oxygen levels are significantly lower than in normal tissues. Hypoxia makes chemo-radiation therapeutics less effective and renders the metastatic potential more favorable. Emerging research has found that the transcriptional expression of hypoxia-inducible factor-1alpha (HIF-1α) promotes the transcription of vascular endothelial growth factor A (VEGF-A) and Hexokinase-I (HK-I), which are associated to cellular growth, angiogenesis, and metastatic invasion in many malignancies. However, it is still unclear whether VEGFA and HK-I expression has any influence on survival based on the intrinsic subtypes of breast cancer. Their prognostic significance remains a debatable topic. In the present study, quantitative Real-time polymerase chain reaction (qRT-PCR) was employed to check the relative expression of HIF-1α, VEGF-A and HK-I. The hazard ratios (HR) of breast cancer-specific and overall mortality were calculated using Cox proportional hazards model, which were adjusted for demographic, clinicopathological, and associated molecular variables, as well as the diagnosis year. The relative mRNA expression levels of HIF-1α (p = 0.0010) and VEGFA (p = 0.0119) were significantly higher in tumor tissues. The expression of both HIF-1α (p = 0.0111) and VEGFA (p = 0.0078) was higher in the TNBC group of breast cancers, while HK-I (p = 0.0106) was higher in ER/PR-positive, HER2-negative group. HIF-1α and HK-I overexpression were associated with a higher likelihood of survival, while overexpression of VEGFA was associated with a low survival rate, although it was not statistically significant.https://doi.org/10.1186/s41231-023-00135-x |
| spellingShingle | Muzamil Farooq Gh. Rasool Bhat Syed Besina Natasha Thakur Sheikh Zahoor Rafiq A. Rather Ifra Mushtaq Sadaf Dar Bilal Rah Ajaz A. Bhat Muzafar A. Macha Dil Afroze Expression of HIF-1α and markers of angiogenesis and metabolic adaptation in molecular subtypes of breast cancer Translational Medicine Communications |
| title | Expression of HIF-1α and markers of angiogenesis and metabolic adaptation in molecular subtypes of breast cancer |
| title_full | Expression of HIF-1α and markers of angiogenesis and metabolic adaptation in molecular subtypes of breast cancer |
| title_fullStr | Expression of HIF-1α and markers of angiogenesis and metabolic adaptation in molecular subtypes of breast cancer |
| title_full_unstemmed | Expression of HIF-1α and markers of angiogenesis and metabolic adaptation in molecular subtypes of breast cancer |
| title_short | Expression of HIF-1α and markers of angiogenesis and metabolic adaptation in molecular subtypes of breast cancer |
| title_sort | expression of hif 1α and markers of angiogenesis and metabolic adaptation in molecular subtypes of breast cancer |
| url | https://doi.org/10.1186/s41231-023-00135-x |
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