Abstract
BackgroundEssential molecular pathways such as the MAPK pathway, NO system, or the influence of PIK3CA as an oncogene are known to regulate fundamental signalling networks. However, few knowledge about their role in the occurrence of wound healing disorders (WHD) following radiation therapy (RT) exists. This study aims to evaluate the expression profiles of specific molecular pathway marker genes.MethodsExpression profiles of the genes encoding MAPK, NOS1, NOS3, and PIK3CA were analyzed, by RT-PCR, in specimens from patients with and without a history of RT to the head and neck. Clinical data on the occurrence of cervical WHDs were analyzed.ResultsExpression analysis of patients with postoperative WHDs revealed a significant increase in MAPK expression compared to the control group without occurrence of postoperative WHDs. PIK3CA showed a significantly increased expression in patients with a history of RT. Expression analysis of all other investigated genes did not reveal significant differences.ConclusionsThis current study is able to show the influence of RT on different molecular pathways. This underlines the crucial role of specific molecular networks, responsible for the occurrence of long-term radiation toxicity such as WHDs. Additional studies should be carried out to identify possible starting points for therapeutic interventions.
Highlights
Essential molecular pathways such as the mitogen-activated protein kinase (MAPK) pathway, Nitric oxide (NO) system, or the influence of PIK3CA as an oncogene are known to regulate fundamental signalling networks
This study aims to evaluate the expression of nitric oxide synthase (NOS) isoforms, PIK3CA, and MAPK in a PCR-based study
Expression analysis of patients with postoperative wound healing disorders (WHD) revealed a significant increase in MAPK expression compared to the control group without occurrence of postoperative WHDs (p = .043)
Summary
Essential molecular pathways such as the MAPK pathway, NO system, or the influence of PIK3CA as an oncogene are known to regulate fundamental signalling networks. Few knowledge about their role in the occurrence of wound healing disorders (WHD) following radiation therapy (RT) exists. In an interdisciplinary and individual oncological treatment concept for cancers of the oral cavity, Radiation Therapy (RT) is next to the surgical resection, and chemotherapy one of the most important columns for local and regional disease control. RT is accompanied with multiple side effects, which can be subdivided in short- and long-term radiation associated toxicity. In cases, when patients received RT preoperatively in a neoadjuvant setting or in cases of disease recurrence, surgeons have to deal with wound healing disorders (WHD). The influence of comorbidities such as protein calorie malnutrition, diabetes, and steroid use, which might be accompanied with impaired wound healing have all been shown to be associated with an reduced NOS expression [13, 14]. Wang and co-workers were able to show, that NO production by dermal fibroblasts could be important during inflammatory stages of wound healing after skin injury [15]
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