The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma
Aberrant SRC expression and activation is frequently detected in multiple cancers, and hence, targeting SRC has emerged as a promising therapeutic strategy. Different SRC inhibitors have demonstrated potent anti-tumor activity in preclinical models, although they largely lack clinical efficacy as mo...
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Format: | Article |
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MDPI AG
2019-10-01
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Series: | Cancers |
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Online Access: | https://www.mdpi.com/2072-6694/11/11/1644 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Francisco Hermida-Prado Rocío Granda-Díaz Nagore del-Río-Ibisate M. Ángeles Villaronga Eva Allonca Irati Garmendia Luis M. Montuenga René Rodríguez Aitana Vallina César Alvarez-Marcos Juan P. Rodrigo Juana M. García-Pedrero |
spellingShingle |
Francisco Hermida-Prado Rocío Granda-Díaz Nagore del-Río-Ibisate M. Ángeles Villaronga Eva Allonca Irati Garmendia Luis M. Montuenga René Rodríguez Aitana Vallina César Alvarez-Marcos Juan P. Rodrigo Juana M. García-Pedrero The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma Cancers head and neck squamous cell carcinoma immunohistochemistry src prognosis larynx pharynx |
author_facet |
Francisco Hermida-Prado Rocío Granda-Díaz Nagore del-Río-Ibisate M. Ángeles Villaronga Eva Allonca Irati Garmendia Luis M. Montuenga René Rodríguez Aitana Vallina César Alvarez-Marcos Juan P. Rodrigo Juana M. García-Pedrero |
author_sort |
Francisco Hermida-Prado |
title |
The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma |
title_short |
The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma |
title_full |
The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma |
title_fullStr |
The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma |
title_full_unstemmed |
The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma |
title_sort |
differential impact of src expression on the prognosis of patients with head and neck squamous cell carcinoma |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2019-10-01 |
description |
Aberrant SRC expression and activation is frequently detected in multiple cancers, and hence, targeting SRC has emerged as a promising therapeutic strategy. Different SRC inhibitors have demonstrated potent anti-tumor activity in preclinical models, although they largely lack clinical efficacy as monotherapy in late-stage solid tumors, including head and neck squamous cell carcinomas (HNSCC). Adequate selection and stratification of patients who may respond to and benefit from anti-SRC therapies is therefore needed to guide clinical trials and treatment efficacy. This study investigates the prognostic significance of active SRC expression in a homogeneous cohort of 122 human papillomavirus (HPV)-negative, surgically treated HNSCC patients. Immunohistochemical evaluation of the active form of SRC by means of anti-SRC Clone 28 monoclonal antibody was specifically performed and subsequently correlated with clinical data. The expression of p-SRC (Tyr419), total SRC, and downstream SRC effectors was also analyzed. Our results uncovered striking differences in the prognostic relevance of SRC expression in HNSCC patients depending on the tumor site. Active SRC expression was found to significantly associate with advanced disease stages, presence of lymph node metastasis, and tumor recurrences in patients with laryngeal tumors, but not in the pharyngeal subgroup. Multivariate Cox analysis further revealed active SRC expression as an independent predictor of cancer-specific mortality in patients with laryngeal carcinomas. Concordantly, expression of p-SRC (Tyr419) and the SRC substrates focal adhesion kinase (FAK) and the Arf GTPase-activating protein ASAP1 also showed specific associations with poor prognosis in the larynx. These findings could have important implications in ongoing Src family kinase (SFK)-based clinical trials, as these new criteria could help to improve patient selection and develop biomarker-stratified trials. |
topic |
head and neck squamous cell carcinoma immunohistochemistry src prognosis larynx pharynx |
url |
https://www.mdpi.com/2072-6694/11/11/1644 |
work_keys_str_mv |
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doaj-f528ed071d9b42bd933de165de6d1f0e2020-11-24T21:19:13ZengMDPI AGCancers2072-66942019-10-011111164410.3390/cancers11111644cancers11111644The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell CarcinomaFrancisco Hermida-Prado0Rocío Granda-Díaz1Nagore del-Río-Ibisate2M. Ángeles Villaronga3Eva Allonca4Irati Garmendia5Luis M. Montuenga6René Rodríguez7Aitana Vallina8César Alvarez-Marcos9Juan P. Rodrigo10Juana M. García-Pedrero11Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011 Oviedo, SpainDepartment of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011 Oviedo, SpainDepartment of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011 Oviedo, SpainDepartment of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011 Oviedo, SpainDepartment of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011 Oviedo, SpainProgram in Solid Tumors, Center for Applied Medical Research (CIMA); Department of Pathology, Anatomy and Physiology, University of Navarra, and Navarra’s Health Research Institute (IDISNA), 31008 Pamplona, SpainCiber de Cáncer, CIBERONC, Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, SpainDepartment of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011 Oviedo, SpainDepartment of Pathology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011 Oviedo, SpainDepartment of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011 Oviedo, SpainDepartment of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011 Oviedo, SpainDepartment of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011 Oviedo, SpainAberrant SRC expression and activation is frequently detected in multiple cancers, and hence, targeting SRC has emerged as a promising therapeutic strategy. Different SRC inhibitors have demonstrated potent anti-tumor activity in preclinical models, although they largely lack clinical efficacy as monotherapy in late-stage solid tumors, including head and neck squamous cell carcinomas (HNSCC). Adequate selection and stratification of patients who may respond to and benefit from anti-SRC therapies is therefore needed to guide clinical trials and treatment efficacy. This study investigates the prognostic significance of active SRC expression in a homogeneous cohort of 122 human papillomavirus (HPV)-negative, surgically treated HNSCC patients. Immunohistochemical evaluation of the active form of SRC by means of anti-SRC Clone 28 monoclonal antibody was specifically performed and subsequently correlated with clinical data. The expression of p-SRC (Tyr419), total SRC, and downstream SRC effectors was also analyzed. Our results uncovered striking differences in the prognostic relevance of SRC expression in HNSCC patients depending on the tumor site. Active SRC expression was found to significantly associate with advanced disease stages, presence of lymph node metastasis, and tumor recurrences in patients with laryngeal tumors, but not in the pharyngeal subgroup. Multivariate Cox analysis further revealed active SRC expression as an independent predictor of cancer-specific mortality in patients with laryngeal carcinomas. Concordantly, expression of p-SRC (Tyr419) and the SRC substrates focal adhesion kinase (FAK) and the Arf GTPase-activating protein ASAP1 also showed specific associations with poor prognosis in the larynx. These findings could have important implications in ongoing Src family kinase (SFK)-based clinical trials, as these new criteria could help to improve patient selection and develop biomarker-stratified trials.https://www.mdpi.com/2072-6694/11/11/1644head and neck squamous cell carcinomaimmunohistochemistrysrcprognosislarynxpharynx |