Importance of CXCL12 and CXCR4 in radiotherapy of head and neck cancer, considering the association with HPV-infection

Tehrany, Narges

dc.contributor.advisor	Burfeind, Peter Prof. Dr.
dc.contributor.author	Tehrany, Narges
dc.date.accessioned	2015-09-10T09:44:11Z
dc.date.available	2015-09-10T09:44:11Z
dc.date.issued	2015-09-10
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0023-9616-2
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-5261
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	610
dc.title	Importance of CXCL12 and CXCR4 in radiotherapy of head and neck cancer, considering the association with HPV-infection	de
dc.type	doctoralThesis	de
dc.contributor.referee	Reichardt, Holger Prof. Dr.
dc.date.examination	2015-08-11
dc.description.abstracteng	p16INK4A expression is an important, independent prognostic marker in HNSCC patients. We observed a strong correlation between tumour HPV status, particularly HPV-16, and p16INK4A expression. Accordingly, our data clearly revealed that p16INK4A expression may be a more powerful marker for predicting prognosis than HPV DNA detection from archived FFPE tumour tissues. The improved OS seen in HNSCC patients with positive p16INK4A expression are thought to be independent of the treatment approach. However, in this study we found that the combination of HPV/p16INK4A positivity and HGAOT as treatment-related toxicities may have an additional effect on improved treatment outcomes and OS of HNSCC patients. Morover, p16INK4A expression is more important for patients without HGAOT. For clinicians, the combined IHC report of p16INK4A expression from the pathology laboratory and the analysis of acute organ toxicity of patients during therapy or even seen after therapy at follow-up appointments could provide important prognostic information for the individual patient and also become the basis of treatment decisions in the future. In this study, we presented clinical and experimental data, underscoring the prognostic value of CXCL12 and CXCR4 in HNSCC patients treated with R(C)T. immunohistochemical analysis of HNSCC biopsies showed that the expression of CXCR4 alone in tumour tissue was a negative predictor for patients, while the expression of CXCL12 was associated with improved OS. We evaluated CXCR4 as a predictive indicator for HNSCC patients with poor prognosis with regard to reduced DMFS and also investigated its biological relevance in the migratory capacity of HNSCC tumour cell lines in a CXCL12 gradient. CXCL12 had a specific effect on migration of HNSCC cells that does not stem to enhanced proliferation. Additionally, we were able to show that CXCL12 also induces irradiated HNSCC cells to migrate, whereas this tendency was significantly reduced in a dose-dependent manner by irradiation. As shown by an experiment in the in vitro study, CXCR4 significantly induces the migration of CXCR4-positive tumour cells and promotes the progression of distant metastases in our in vivo analysis. Accordingly, these results indicate that the CXCL12/CXCR4-pathway is functionally relevant in head and neck cancer cell lines, which in turn supports the clinical data. we have also demonstrated that different indicators and biomarkers are of independent prognostic value in HNSCC. These results can also lead us to a new efficient treatment strategy, in which the intensity of CT or extent of the irradiated area can be altered while maintaining good tumour control with the ability to rationally personalise therapy to advance therapeutic outcomes.	de
dc.contributor.coReferee	Wolff, Andreas PD Dr.
dc.subject.eng	HPV	de
dc.subject.eng	CXCL12	de
dc.subject.eng	CXCR4	de
dc.subject.eng	radiotherapy	de
dc.subject.eng	metastasis	de
dc.subject.eng	HNSCC	de
dc.subject.eng	HGAOT	de
dc.subject.eng	tumor cell migration	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0023-9616-2-6
dc.affiliation.institute	Medizinische Fakultät
dc.subject.gokfull	Medizin (PPN619874732)	de
dc.subject.gokfull	Oto-Rhino-Laryngologie (PPN619876220)	de
dc.subject.gokfull	Medizinische Mikrobiologie / Medizinische Virologie / Medizinische Mykologie / Infektionskrankheiten / Hygiene / Impfung / Parasitologie / Tropenmedizin - Allgemein- und Gesamtdarstellungen (PPN619875356)	de
dc.subject.gokfull	Immunologie / Allergologie / Umweltmedizin / Medizinische Ökologie - Allgemein- und Gesamtdarstellungen (PPN619875445)	de
dc.identifier.ppn	834825414

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