P4HA1: A single-gene surrogate of hypoxia signatures in oral squamous cell carcinoma patients

Background and purpose: Hypoxia gene expression signatures are of high prognostic value for head and neck cancer patients. Recently, the prognostic information of a multiple-gene hypoxia signature was found to be provided by the mRNA level of P4HA1 alone (Tawk et al., 2016). Therefore, we studied th...

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Main Authors: Matthias Kappler, Johanna Kotrba, Tom Kaune, Matthias Bache, Swetlana Rot, Daniel Bethmann, Henri Wichmann, Antje Güttler, Udo Bilkenroth, Susanne Horter, Lisa Gallwitz, Jacqueline Kessler, Thomas Greither, Helge Taubert, Alexander W. Eckert, Dirk Vordermark
Format: Article
Language:English
Published: Elsevier 2017-08-01
Series:Clinical and Translational Radiation Oncology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S240563081730023X
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author Matthias Kappler
Johanna Kotrba
Tom Kaune
Matthias Bache
Swetlana Rot
Daniel Bethmann
Henri Wichmann
Antje Güttler
Udo Bilkenroth
Susanne Horter
Lisa Gallwitz
Jacqueline Kessler
Thomas Greither
Helge Taubert
Alexander W. Eckert
Dirk Vordermark
author_facet Matthias Kappler
Johanna Kotrba
Tom Kaune
Matthias Bache
Swetlana Rot
Daniel Bethmann
Henri Wichmann
Antje Güttler
Udo Bilkenroth
Susanne Horter
Lisa Gallwitz
Jacqueline Kessler
Thomas Greither
Helge Taubert
Alexander W. Eckert
Dirk Vordermark
author_sort Matthias Kappler
collection DOAJ
description Background and purpose: Hypoxia gene expression signatures are of high prognostic value for head and neck cancer patients. Recently, the prognostic information of a multiple-gene hypoxia signature was found to be provided by the mRNA level of P4HA1 alone (Tawk et al., 2016). Therefore, we studied the prognostic value of P4HA1 in an independent cohort of oral squamous cell carcinoma (OSCC) patients. Material and methods: Frozen tumor samples of 118 adult OSCC patients were analysed for P4HA1 mRNA level by quantitative real-time TaqMan™ PCR analysis. Kaplan-Meier analysis and Cox’s regression analysis were performed to characterize the prognostic impact of P4HA1 mRNA level in OSCC patients. Results: The analyzed patient cohort was divided into four subgroups according to the quartiles of the P4HA1 mRNA levels. The highest intratumoral P4HA1 mRNA level was significantly correlated with a poor overall survival (RR = 2.2; P = 0.04) and an increased risk of locoregional recurrence (RR = 4.8; P = 0.02). In patients who received radiotherapy (n = 82) highest intratumoral P4HA1 mRNA level was significantly correlated with a poor overall survival (RR = 3.4; P = 0.01) and an increased risk of locoregional recurrence (RR = 10.3; P = 0.005). Moreover, significant correlations between the P4HA1 mRNA level and the mRNA level of several EMT and stem cell markers were found. Conclusions: A high P4HA1 mRNA level, as a single-gene surrogate of hypoxia, is an independent prognostic marker for the overall survival and locoregional recurrence of OSCC patients.
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spelling doaj.art-3dd1265248cc4489be0beca9bab78de42022-12-21T22:21:44ZengElsevierClinical and Translational Radiation Oncology2405-63082017-08-015C61110.1016/j.ctro.2017.05.002P4HA1: A single-gene surrogate of hypoxia signatures in oral squamous cell carcinoma patientsMatthias Kappler0Johanna Kotrba1Tom Kaune2Matthias Bache3Swetlana Rot4Daniel Bethmann5Henri Wichmann6Antje Güttler7Udo Bilkenroth8Susanne Horter9Lisa Gallwitz10Jacqueline Kessler11Thomas Greither12Helge Taubert13Alexander W. Eckert14Dirk Vordermark15Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), GermanyDepartment of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), GermanyDepartment of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), GermanyDepartment of Radiotherapy, Martin Luther University Halle-Wittenberg, Halle (Saale), GermanyDepartment of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), GermanyInstitute of Pathology, Martin Luther University Halle-Wittenberg, Halle (Saale), GermanyDepartment of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), GermanyDepartment of Radiotherapy, Martin Luther University Halle-Wittenberg, Halle (Saale), GermanyInstitute of Pathology, Eisleben, GermanyDepartment of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), GermanyCenter for Reproductive Medicine and Andrology, Martin Luther University Halle-Wittenberg, GermanyDepartment of Radiotherapy, Martin Luther University Halle-Wittenberg, Halle (Saale), GermanyCenter for Reproductive Medicine and Andrology, Martin Luther University Halle-Wittenberg, GermanyClinic of Urology and Pediatric Urology, University Hospital Erlangen, Erlangen, GermanyDepartment of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), GermanyDepartment of Radiotherapy, Martin Luther University Halle-Wittenberg, Halle (Saale), GermanyBackground and purpose: Hypoxia gene expression signatures are of high prognostic value for head and neck cancer patients. Recently, the prognostic information of a multiple-gene hypoxia signature was found to be provided by the mRNA level of P4HA1 alone (Tawk et al., 2016). Therefore, we studied the prognostic value of P4HA1 in an independent cohort of oral squamous cell carcinoma (OSCC) patients. Material and methods: Frozen tumor samples of 118 adult OSCC patients were analysed for P4HA1 mRNA level by quantitative real-time TaqMan™ PCR analysis. Kaplan-Meier analysis and Cox’s regression analysis were performed to characterize the prognostic impact of P4HA1 mRNA level in OSCC patients. Results: The analyzed patient cohort was divided into four subgroups according to the quartiles of the P4HA1 mRNA levels. The highest intratumoral P4HA1 mRNA level was significantly correlated with a poor overall survival (RR = 2.2; P = 0.04) and an increased risk of locoregional recurrence (RR = 4.8; P = 0.02). In patients who received radiotherapy (n = 82) highest intratumoral P4HA1 mRNA level was significantly correlated with a poor overall survival (RR = 3.4; P = 0.01) and an increased risk of locoregional recurrence (RR = 10.3; P = 0.005). Moreover, significant correlations between the P4HA1 mRNA level and the mRNA level of several EMT and stem cell markers were found. Conclusions: A high P4HA1 mRNA level, as a single-gene surrogate of hypoxia, is an independent prognostic marker for the overall survival and locoregional recurrence of OSCC patients.http://www.sciencedirect.com/science/article/pii/S240563081730023XP4HA1SurvivalHypoxiaOSCCRecurrence
spellingShingle Matthias Kappler
Johanna Kotrba
Tom Kaune
Matthias Bache
Swetlana Rot
Daniel Bethmann
Henri Wichmann
Antje Güttler
Udo Bilkenroth
Susanne Horter
Lisa Gallwitz
Jacqueline Kessler
Thomas Greither
Helge Taubert
Alexander W. Eckert
Dirk Vordermark
P4HA1: A single-gene surrogate of hypoxia signatures in oral squamous cell carcinoma patients
Clinical and Translational Radiation Oncology
P4HA1
Survival
Hypoxia
OSCC
Recurrence
title P4HA1: A single-gene surrogate of hypoxia signatures in oral squamous cell carcinoma patients
title_full P4HA1: A single-gene surrogate of hypoxia signatures in oral squamous cell carcinoma patients
title_fullStr P4HA1: A single-gene surrogate of hypoxia signatures in oral squamous cell carcinoma patients
title_full_unstemmed P4HA1: A single-gene surrogate of hypoxia signatures in oral squamous cell carcinoma patients
title_short P4HA1: A single-gene surrogate of hypoxia signatures in oral squamous cell carcinoma patients
title_sort p4ha1 a single gene surrogate of hypoxia signatures in oral squamous cell carcinoma patients
topic P4HA1
Survival
Hypoxia
OSCC
Recurrence
url http://www.sciencedirect.com/science/article/pii/S240563081730023X
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