Higher Expressions of SHH and AR Are Associated with a Positive Receptor Status and Have Impact on Survival in a Cohort of Croatian Breast Cancer Patients
Breast cancers (BC) are usually classified into four molecular subtypes according to the expression of estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2) receptors and proliferation marker Ki-67. Despite available anti-hormonal therapies and due to the inherent propensity o...
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MDPI AG
2022-10-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/10/1559 |
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| author | Ivan Budimir Čedna Tomasović-Lončarić Kristina Kralik Josipa Čonkaš Domagoj Eljuga Rado Žic Božo Gorjanc Hrvoje Tucaković Doroteja Caktaš Josip Jaman Valentino Lisek Zlatko Vlajčić Krešimir Martić Petar Ozretić |
| author_facet | Ivan Budimir Čedna Tomasović-Lončarić Kristina Kralik Josipa Čonkaš Domagoj Eljuga Rado Žic Božo Gorjanc Hrvoje Tucaković Doroteja Caktaš Josip Jaman Valentino Lisek Zlatko Vlajčić Krešimir Martić Petar Ozretić |
| author_sort | Ivan Budimir |
| collection | DOAJ |
| description | Breast cancers (BC) are usually classified into four molecular subtypes according to the expression of estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2) receptors and proliferation marker Ki-67. Despite available anti-hormonal therapies and due to the inherent propensity of some subtypes to develop metastasis, there is a permanent need to discover new prognostic and predictive biomarkers, as well as therapeutic targets for BC. In this study, we used immunohistochemical staining to determine the expression of androgen receptor (AR) and sonic hedgehog protein (SHH), the main ligand of the Hedgehog-GLI (HH-GLI) signaling pathway, in 185 archival primary BC tissue samples and correlated it with clinicopathological characteristics, molecular subtypes, receptors statuses, and survival in a cohort of Croatian BC patients. Results showed that higher SHH and AR expressions were associated with positive receptor status, but increased SHH expression had a negative impact on survival in receptor-negative BCs. On the contrary, higher AR expression was mostly protective. However, multivariate analysis showed that only higher AR expression could be considered as an independent prognostic biomarker for poorer overall survival in triple-negative breast cancer patients (TNBC) (HR 10.9, 95% CI 1.43–83.67; <i>p</i> = 0.021), what could be Croatian population-related. SHH could be a potential target for treating TNBCs and HER2-enriched BCs, in cases where HH-GLI signaling is canonical (SHH-dependent). |
| first_indexed | 2024-03-09T12:13:26Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T12:13:26Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-fbf25e9fbc3545a480612f2cb43ec55c2023-11-30T22:50:27ZengMDPI AGLife2075-17292022-10-011210155910.3390/life12101559Higher Expressions of SHH and AR Are Associated with a Positive Receptor Status and Have Impact on Survival in a Cohort of Croatian Breast Cancer PatientsIvan Budimir0Čedna Tomasović-Lončarić1Kristina Kralik2Josipa Čonkaš3Domagoj Eljuga4Rado Žic5Božo Gorjanc6Hrvoje Tucaković7Doroteja Caktaš8Josip Jaman9Valentino Lisek10Zlatko Vlajčić11Krešimir Martić12Petar Ozretić13Department of Plastic, Reconstructive and Aesthetic Surgery, Dubrava University Hospital, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaClinical Department of Pathology and Cytology, Dubrava University Hospital, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Medical Statistics and Medical Informatics, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, CroatiaDivision of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, CroatiaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Dubrava University Hospital, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Dubrava University Hospital, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Dubrava University Hospital, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Dubrava University Hospital, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Dubrava University Hospital, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Dubrava University Hospital, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Abdominal Surgery, Dubrava University Hospital, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Dubrava University Hospital, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Dubrava University Hospital, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDivision of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, CroatiaBreast cancers (BC) are usually classified into four molecular subtypes according to the expression of estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2) receptors and proliferation marker Ki-67. Despite available anti-hormonal therapies and due to the inherent propensity of some subtypes to develop metastasis, there is a permanent need to discover new prognostic and predictive biomarkers, as well as therapeutic targets for BC. In this study, we used immunohistochemical staining to determine the expression of androgen receptor (AR) and sonic hedgehog protein (SHH), the main ligand of the Hedgehog-GLI (HH-GLI) signaling pathway, in 185 archival primary BC tissue samples and correlated it with clinicopathological characteristics, molecular subtypes, receptors statuses, and survival in a cohort of Croatian BC patients. Results showed that higher SHH and AR expressions were associated with positive receptor status, but increased SHH expression had a negative impact on survival in receptor-negative BCs. On the contrary, higher AR expression was mostly protective. However, multivariate analysis showed that only higher AR expression could be considered as an independent prognostic biomarker for poorer overall survival in triple-negative breast cancer patients (TNBC) (HR 10.9, 95% CI 1.43–83.67; <i>p</i> = 0.021), what could be Croatian population-related. SHH could be a potential target for treating TNBCs and HER2-enriched BCs, in cases where HH-GLI signaling is canonical (SHH-dependent).https://www.mdpi.com/2075-1729/12/10/1559breast cancermolecular subtypesSonic hedgehog proteinandrogen receptorprognostic biomarkerssurvival analysis |
| spellingShingle | Ivan Budimir Čedna Tomasović-Lončarić Kristina Kralik Josipa Čonkaš Domagoj Eljuga Rado Žic Božo Gorjanc Hrvoje Tucaković Doroteja Caktaš Josip Jaman Valentino Lisek Zlatko Vlajčić Krešimir Martić Petar Ozretić Higher Expressions of SHH and AR Are Associated with a Positive Receptor Status and Have Impact on Survival in a Cohort of Croatian Breast Cancer Patients Life breast cancer molecular subtypes Sonic hedgehog protein androgen receptor prognostic biomarkers survival analysis |
| title | Higher Expressions of SHH and AR Are Associated with a Positive Receptor Status and Have Impact on Survival in a Cohort of Croatian Breast Cancer Patients |
| title_full | Higher Expressions of SHH and AR Are Associated with a Positive Receptor Status and Have Impact on Survival in a Cohort of Croatian Breast Cancer Patients |
| title_fullStr | Higher Expressions of SHH and AR Are Associated with a Positive Receptor Status and Have Impact on Survival in a Cohort of Croatian Breast Cancer Patients |
| title_full_unstemmed | Higher Expressions of SHH and AR Are Associated with a Positive Receptor Status and Have Impact on Survival in a Cohort of Croatian Breast Cancer Patients |
| title_short | Higher Expressions of SHH and AR Are Associated with a Positive Receptor Status and Have Impact on Survival in a Cohort of Croatian Breast Cancer Patients |
| title_sort | higher expressions of shh and ar are associated with a positive receptor status and have impact on survival in a cohort of croatian breast cancer patients |
| topic | breast cancer molecular subtypes Sonic hedgehog protein androgen receptor prognostic biomarkers survival analysis |
| url | https://www.mdpi.com/2075-1729/12/10/1559 |
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