Salivary IL-8 as a putative predictive biomarker of radiotherapy response in head and neck cancer patients.

OBJECTIVES: Ionizing radiation increases the expression of a number of salivary proteins involved in immunoregulatory networks related to infection, injury, inflammation, and cancer. Our main objective was to analyze whether there are significant differences in salivary cytokines before and after radiotherapy and whether any of them are associated to better outcomes after radiotherapy serving as a potential predictive biomarker of response to the treatment. MATERIALS AND METHODS: We analyzed a panel of eight salivary markers (IL-4, IL-6, IL-8, and IL-10; MCP-1; TNF-α; VEGF; and EGF) in a group of HNC patients (N = 30), before and after irradiation treatment pre- and post-RT. We also compared these results with a group of healthy controls (N = 37). In both groups, we used stimulated saliva and we performed immunoassays based on multi-analyte profiling technology (Luminex xMAP). RESULTS: In our group of 30 HNC patients, 24 of them showed a good clinical response after radiotherapy treatment while 6 cases did not respond to radiotherapy. The data revealed a post-treatment increase in multiple cytokines in the stimulated saliva of HNC patients; the increases in IL-8 and MCP-1 were statistically significant (p ≤ 0.001 and p ≤ 0.0001, respectively). Analysis of receiver operating characteristic curves indicated the strong potential of IL-8 as a predictive biomarker of RT good outcomes (area under the curve = 0.84; p = 0.018). CONCLUSIONS: After analyzing the panel of salivary cytokines, IL-8 showed the best association to the response to radiotherapy; in this sense, low IL-8 levels in the saliva of HNC patients before receiving irradiation therapy are associated with positive RT outcomes. CLINICAL RELEVANCE: Salivary IL-8 expression in HNC patients undergoing RT may serve as a potential predictive biomarker of response to the treatment.

Salivary Cytokines in patients with Head and Neck Cancer (HNC) treated with Radiotherapy.

BACKGROUND: Head and Neck cancer (HNC) is the sixth most common cancer in the world. The 5-year survival rate depends on early diagnosis and appropriate therapy. Typically, late diagnosis requires not only surgical intervention, but also radiotherapy treatment combined or not with chemotherapy. Ionizing radiation is known to increase the expression of a number of cytokines involved in inflammation, wound healing and toxicity areas. Salivary cytokines have promising features to be used as biomarkers for disease screening and outcome prediction in this malignancy. The aim of this article is to analyze the role of salivary inflammatory response elements in HNC patients treated with radiotherapy, their modulation and association with the treatment outcome. MATERIAL AND METHODS: A bibliographical search was performed on Pubmed, Cochrane and Embase using the following keywords: cytokines, saliva, head and neck cancer, radiotherapy. The cut-off point for the research were scientific papers published over the last 10 years. After a two-step selection process, 15 articles were identified and subjected to review. RESULTS: Radiotherapy treatment was shown to influence a number of salivary cytokines. A trend towards a growth of IL-1ß, IL-6, IL-8, MCP-1, and TNF-α levels was observed and it correlated with the irradiation dose. CONCLUSIONS: The analysis of salivary cytokines could be a useful biomarker for predicting radiotherapy outcome in HNC. However, large-scale investigations are required to validate the use of these cytokines in predicting and diagnosing HNC, as well as evaluating the response to the treatment. Key words:Cytokines, saliva, head and neck cancer, radiotherapy.

Salivary inflammatory proteins in patients with oral potentially malignant disorders.

Cytokines are a group of small proteins involved in the regulation of infection, immune responses and inflammation. Since altered cytokine responsiveness has been linked to Oral Squamous Cell Carcinoma (OSCC), research to date indicates the possibility of using salivary pro- and anti-inflammatory proteins for screening of oral disorders. OSCC is a multistep neoplasia in which many genetic and epigenetic changes have been correlated to cancerous transformation of oral potentially malignant disorders (OPMD) such as oral leukoplakia, erythroplakia and lichen planus. The goal of the innovative salivary diagnostics is the identification of a single or multiple biomarkers that will serve as a clinical test facilitating the diagnosis of patients predisposed to develop OSCC. Based on scientific literature review, this article summarizes the results from nine articles, all of them being case-control studies where TNF-α, IL-1ß, IL-6 and IL-8 were considered possible indicators of malignant transformation. Key words:Interleukins, saliva, oral premalignant lesions.