Prognostic value of hypoxia-responsive gene expression profile in patients diagnosed with head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a disease associated with a severe mortality and high risk of distant metastasis and local recurrence. Currently, surgery and radiotherapy are the main treatment modes, however, therapeutic efficacy of radiotherapy is linked to tumor resistance. Hypox...

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Main Authors: Natasa Matic, Lina Pettersson, Felicia Sellebjerg, Lina Lindberg, Karin Roberg, Emilia Wiechec
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:Translational Oncology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1936523323002279
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author Natasa Matic
Lina Pettersson
Felicia Sellebjerg
Lina Lindberg
Karin Roberg
Emilia Wiechec
author_facet Natasa Matic
Lina Pettersson
Felicia Sellebjerg
Lina Lindberg
Karin Roberg
Emilia Wiechec
author_sort Natasa Matic
collection DOAJ
description Head and neck squamous cell carcinoma (HNSCC) is a disease associated with a severe mortality and high risk of distant metastasis and local recurrence. Currently, surgery and radiotherapy are the main treatment modes, however, therapeutic efficacy of radiotherapy is linked to tumor resistance. Hypoxia has been shown to affect outcome of radiotherapy in HNSCC patients. The aim of this study was to verify the expression of the previously identified hypoxia-responsive genes (CA9, CASP14, LOX, GLUT3, SERPINE1, AREG, EREG, CCNB1 and KIF14) in HNSCC patient material as well as assess their prognostic potential. Tumor biopsies obtained before start of radiotherapy from 32 HNSCC patients classified as responders or non-responders were investigated in this study. The mRNA expression was quantified using RT-qPCR. The mRNA expression of CA9, SERPINE1 and KIF14 was significantly higher in the analyzed patient material compared with the non-cancerous oral tissue. Moreover, the KIF14 mRNA expression was significantly higher in the responder group compared to non-responders. Further studies demonstrated that knockdown of KIF14 reverses its radiosensitizing capability. Additionally, low expression of KIF14 mRNA correlated with significantly shorter OS (overall survival). In conclusion, our results suggest that KIF14 might be a useful prognostic and predictive marker in HNSCC.
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spelling doaj.art-54e55084fb854c1e82eaa417f5b8c2cb2023-12-03T05:40:31ZengElsevierTranslational Oncology1936-52332024-01-0139101841Prognostic value of hypoxia-responsive gene expression profile in patients diagnosed with head and neck squamous cell carcinomaNatasa Matic0Lina Pettersson1Felicia Sellebjerg2Lina Lindberg3Karin Roberg4Emilia Wiechec5Department of Otorhinolaryngology in Linköping, Anaesthetics, Operations and Specialty Surgery Center, Region Östergötland, Linköping 58185, SwedenDepartment of Biomedical and Clinical Sciences, Division of Cell Biology, Linköping University, Linköping 58185, SwedenDepartment of Biomedical and Clinical Sciences, Division of Cell Biology, Linköping University, Linköping 58185, SwedenDepartment of Biomedical and Clinical Sciences, Division of Cell Biology, Linköping University, Linköping 58185, SwedenDepartment of Otorhinolaryngology in Linköping, Anaesthetics, Operations and Specialty Surgery Center, Region Östergötland, Linköping 58185, Sweden; Department of Biomedical and Clinical Sciences, Division of Cell Biology, Linköping University, Linköping 58185, Sweden; Corresponding authors.Department of Otorhinolaryngology in Linköping, Anaesthetics, Operations and Specialty Surgery Center, Region Östergötland, Linköping 58185, Sweden; Department of Biomedical and Clinical Sciences, Division of Cell Biology, Linköping University, Linköping 58185, Sweden; Corresponding authors.Head and neck squamous cell carcinoma (HNSCC) is a disease associated with a severe mortality and high risk of distant metastasis and local recurrence. Currently, surgery and radiotherapy are the main treatment modes, however, therapeutic efficacy of radiotherapy is linked to tumor resistance. Hypoxia has been shown to affect outcome of radiotherapy in HNSCC patients. The aim of this study was to verify the expression of the previously identified hypoxia-responsive genes (CA9, CASP14, LOX, GLUT3, SERPINE1, AREG, EREG, CCNB1 and KIF14) in HNSCC patient material as well as assess their prognostic potential. Tumor biopsies obtained before start of radiotherapy from 32 HNSCC patients classified as responders or non-responders were investigated in this study. The mRNA expression was quantified using RT-qPCR. The mRNA expression of CA9, SERPINE1 and KIF14 was significantly higher in the analyzed patient material compared with the non-cancerous oral tissue. Moreover, the KIF14 mRNA expression was significantly higher in the responder group compared to non-responders. Further studies demonstrated that knockdown of KIF14 reverses its radiosensitizing capability. Additionally, low expression of KIF14 mRNA correlated with significantly shorter OS (overall survival). In conclusion, our results suggest that KIF14 might be a useful prognostic and predictive marker in HNSCC.http://www.sciencedirect.com/science/article/pii/S1936523323002279Head and neck cancerHypoxiaRadiotherapyBiomarkerPrognostic factorKIF14
spellingShingle Natasa Matic
Lina Pettersson
Felicia Sellebjerg
Lina Lindberg
Karin Roberg
Emilia Wiechec
Prognostic value of hypoxia-responsive gene expression profile in patients diagnosed with head and neck squamous cell carcinoma
Translational Oncology
Head and neck cancer
Hypoxia
Radiotherapy
Biomarker
Prognostic factor
KIF14
title Prognostic value of hypoxia-responsive gene expression profile in patients diagnosed with head and neck squamous cell carcinoma
title_full Prognostic value of hypoxia-responsive gene expression profile in patients diagnosed with head and neck squamous cell carcinoma
title_fullStr Prognostic value of hypoxia-responsive gene expression profile in patients diagnosed with head and neck squamous cell carcinoma
title_full_unstemmed Prognostic value of hypoxia-responsive gene expression profile in patients diagnosed with head and neck squamous cell carcinoma
title_short Prognostic value of hypoxia-responsive gene expression profile in patients diagnosed with head and neck squamous cell carcinoma
title_sort prognostic value of hypoxia responsive gene expression profile in patients diagnosed with head and neck squamous cell carcinoma
topic Head and neck cancer
Hypoxia
Radiotherapy
Biomarker
Prognostic factor
KIF14
url http://www.sciencedirect.com/science/article/pii/S1936523323002279
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