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Open AccessArticle

The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma

1
Department 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, Spain
2
Ciber de Cáncer, CIBERONC, Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain
3
Program 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, Spain
4
Department 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, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(11), 1644; https://doi.org/10.3390/cancers11111644
Received: 3 October 2019 / Revised: 21 October 2019 / Accepted: 23 October 2019 / Published: 25 October 2019
(This article belongs to the Special Issue The Role of Src Kinase Family in Cancer)
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. View Full-Text
Keywords: head and neck squamous cell carcinoma; immunohistochemistry; SRC; prognosis; larynx; pharynx head and neck squamous cell carcinoma; immunohistochemistry; SRC; prognosis; larynx; pharynx
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Hermida-Prado, F.; Granda-Díaz, R.; del-Río-Ibisate, N.; Villaronga, M.Á.; Allonca, E.; Garmendia, I.; Montuenga, L.M.; Rodríguez, R.; Vallina, A.; Alvarez-Marcos, C.; Rodrigo, J.P.; García-Pedrero, J.M. The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma. Cancers 2019, 11, 1644.

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