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Changes in circulating microRNAs after radiochemotherapy in head and neck cancer patients.

ABSTRACT: INTRODUCTION: Circulating microRNAs (miRNAs) are easily accessible and have already proven to be useful as prognostic markers in cancer patients. However, their origin and function in the circulation is still under discussion. In the present study we analyzed changes in the miRNAs in blood plasma of head and neck squamous cell carcinoma (HNSCC) patients in response to radiochemotherapy and compared them to the changes in a cell culture model of primary HNSCC cells undergoing simulated anti-cancer therapy. MATERIALS AND METHODS: MiRNA-profiles were analyzed by qRT-PCR arrays in paired blood plasma samples of HNSCC patients before therapy and after two days of treatment. Candidate miRNAs were validated by single qRT-PCR assays. An in vitro radiochemotherapy model using primary HNSCC cell cultures was established to test the possible tumor origin of the circulating miRNAs. Microarray analysis was performed on primary HNSCC cell cultures followed by validation of deregulated miRNAs via qRT-PCR. RESULTS: Unsupervised clustering of the expression profiles using the six most regulated miRNAs (miR-425-5p, miR-21-5p, miR-106b-5p, miR-590-5p, miR-574-3p, miR-885-3p) significantly (p?=?0.012) separated plasma samples collected prior to treatment from plasma samples collected after two days of radiochemotherapy. MiRNA profiling of primary HNSCC cell cultures treated in vitro with radiochemotherapy revealed differentially expressed miRNAs that were also observed to be therapy-responsive in blood plasma of the patients (miR-425-5p, miR-21-5p, miR-106b-5p, miR-93-5p) and are therefore likely to stem from the tumor. Of these candidate marker miRNAs we were able to validate by qRT-PCR a deregulation of eight plasma miRNAs as well as miR-425-5p and miR-93-5p in primary HNSCC cultures after radiochemotherapy. CONCLUSION: Changes in the abundance of circulating miRNAs during radiochemotherapy reflect the therapy response of primary HNSCC cells after an in vitro treatment. Therefore, the responsive miRNAs (miR-425-5p, miR-93-5p) may represent novel biomarkers for therapy monitoring. The prognostic value of this exciting observation requires confirmation using an independent patient cohort that includes clinical follow-up data.

SUBMITTER: Summerer I

PROVIDER: S-EPMC3882107 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Changes in circulating microRNAs after radiochemotherapy in head and neck cancer patients.

Summerer Isolde I Niyazi Maximilian M Unger Kristian K Pitea Adriana A Zangen Verena V Hess Julia J Atkinson Michael J MJ Belka Claus C Moertl Simone S Zitzelsberger Horst H

Radiation oncology (London, England) 20131228

<h4>Introduction</h4>Circulating microRNAs (miRNAs) are easily accessible and have already proven to be useful as prognostic markers in cancer patients. However, their origin and function in the circulation is still under discussion. In the present study we analyzed changes in the miRNAs in blood plasma of head and neck squamous cell carcinoma (HNSCC) patients in response to radiochemotherapy and compared them to the changes in a cell culture model of primary HNSCC cells undergoing simulated ant ...[more]

PMID: 24373621

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Project description:Highlights: Sarcopenia is frequent in patients treated with radiation therapy (RT) or radiochemotherapy (RTCT) for head and neck squamous cell carcinomas. Sarcopenia is associated with poor disease-free survival and overall survival outcomes. Sarcopenia is not associated with a higher rate of treatment-related toxicity. Background: Sarcopenia occurs frequently with the diagnosis of head and neck squamous cell carcinoma (HNSCC). We aimed to assess the impact of sarcopenia on survival among HNSCC patients treated with radiotherapy (RT) or radiochemotherapy (RTCT). Methods: Patients treated between 2014 and 2018 by RT or RTCT with curative intent were prospectively included (NCT02900963). Optimal nutritional support follow-up, including weekly consultation with a dietician and an oncologist and daily weight monitoring, was performed. Sarcopenia was determined by measuring the skeletal muscles at the L3 vertebra on the planning CT scan for radiotherapy. For each treatment group (RT or RTCT), we assessed the prognostic value of sarcopenia for disease-free survival (DFS) and overall survival (OS) and its impact on treatment-related toxicity. Results: Two hundred forty-three HNSCC patients were included: 116 were treated by RT and 127 were treated by RTCT. Before radiotherapy, eight (3.3%) patients were considered malnourished according to albumin, whereas 88 (36.7%) patients were sarcopenic. Overall, sarcopenia was associated with OS and DFS in a multivariate analysis (HR 1.9 [1.1-3.25] and 1.7 [1.06-2.71], respectively). It was similar for patients treated with RT (HR 2.49 [1.26-4.9] for DFS and 2.24 [1.03-4.86] for OS), whereas for patients treated with RTCT sarcopenia was significantly associated with OS and DFS in univariate analysis only. Sarcopenia was not related to higher treatment-related toxicity. Conclusions: Pretherapeutic sarcopenia remains frequent and predicts OS and DFS for non-frail patients treated with curative intent and adequate nutritional support.

Project description:BackgroundThe impacts of radiochemotherapy on peripheral blood cell and lymphocyte cell counts, immunoglobulin (Ig) and complement levels remain unclear. This study aims to investigate the above parameters regulated by radiotherapy (RT), induction chemotherapy (ICT) and concurrent chemotherapy (CCT) in head and neck cancer (HNC) patients.MethodsPatients with non-metastatic HNC treated by conventional intensity-modulated radiation therapy (IMRT) were enrolled in this study. Data of peripheral blood cells, lymphocyte subpopulations, complements and immunoglobulins were collected before, during and after IMRT. And conducted regular follow-up on patients. SPSS (IBM, version 26.0), R (MathSoft, 4.0.3) and Graphpad Prism were used to perform statistical analysis and plot figures.ResultsA total of 126 HNC patients undergoing RT were enrolled in this study. Among them, 44 patients received ICT, 56 patients received CCT, and 123 patients had complete survival information. Number of white blood cells (WBCs), platelets, basophils, total lymphocytes, CD4+ and CD8+ T cells, natural killer (NK) cells, B cells declined significantly during RT. Accordingly, the ratio of help T cells to suppressor T cells (Th/Ts) and the percentages of B cells, CD4+ T cells also declined. There were increased levels of neutrophils and complement 4 (C4) and percentage of NK cells during RT. ICT caused significant reductions of platelets, B cells and immunoglobulin A (IgA). CCT reduced WBCs, red blood cells (RBCs), platelets, hemoglobin (HGB), granulocytes, total lymphocytes, B cells, CD4+ and CD8+ T cells, NK cells and immunoglobulin G (IgG). Generalized linear model (GLM) analysis further confirmed that RT was a risk factor for lower total lymphocytes, B cells, CD4+ and CD8+ T cells, NK cells, Th/Ts ratios, and lower percentages of B cells, CD4+ T cells. ICT contributed to decreased Th/Ts ratios, and immunoglobulin M (IgM) and IgA levels. As for CCT, it was an unfavorable factor for reduced total lymphocytes, B cells, CD4+ and CD8+ T cells, NK cells and IgG. Conversely, complement 3 (C3) or 4 levels were higher in patients treated with RT, ICT or CCT. Importantly, we found that HNC patients with higher lymphocytes or lymphocyte percentages like CD3+, CD4+ and CD8+ T cells before or after RT had a better prognosis. While higher NK cells and NK cell percentage before RT were associated with worse prognosis. In addition, higher levels of C3 and C4 before and after RT were associated with a favorable prognosis. However, higher levels of IgA, immunoglobulin E (IgE), IgG, and IgM before RT were associated with poorer prognosis.ConclusionsTo sum up, chemoradiotherapy resulted in significant alterations in peripheral immune biomarkers which in return influenced HNC patients' survival.

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Changes in circulating microRNAs after radiochemotherapy in head and neck cancer patients.

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Changes in circulating microRNAs after radiochemotherapy in head and neck cancer patients.

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