Abstract

Partial body irradiation during cancer radiotherapy (RT) induces a response of irradiated tissues that could be observed at the level of serum proteome. Here we aimed to characterize the response to RT in group of patients treated because of prostate cancer. Five consecutive blood samples were collected before, during, and after the end of RT in a group of 126 patients who received definitive treatment with a maximum dose of 76 Gy. Serum peptidome, which was profiled in the 2000–16,000 Da range using MALDI-MS. Serum proteins were identified and quantified using the shotgun LC-MS/MS approach. The majority of changes in serum peptidome were detected between pre-treatment samples and samples collected after 3–4 weeks of RT (~25% of registered peptides changed their abundances significantly), yet the intensity of observed changes was not correlated significantly with the degree of acute radiation toxicity or the volume of irradiated tissues. Furthermore, there were a few serum proteins identified, the abundances of which were different in pre-RT and post-RT samples, including immunity and inflammation-related factors. Observed effects were apparently weaker than in comparable groups of head and neck cancer patients in spite of similar radiation doses and volumes of irradiated tissues in both groups. We concluded that changes observed at the level of serum proteome were low for this cohort of prostate cancer patients, although the specific components involved are associated with immunity and inflammation, and reflect the characteristic acute response of the human body to radiation.

Highlights

  • Radiotherapy (RT), either alone or in combination with other treatment modalities, is an effective treatment of patients suffering from different types of cancer which allows the delivery of a cytotoxic dose to the tumor while sparing the structure and function of critical healthy organs

  • Further analysis of intensity modulated RT (IMRT)-related effects in a group of patients suffering from head and neck cancer (head and neck squamous cell carcinoma (HNSCC)) revealed that changes in serum peptidome features were associated with intensity of acute mucosal toxicity and were affected by low-to-medium doses delivered to large volumes of normal tissues [22]

  • We found that only when tissue volume irradiated with a 70 Gy dose was analyzed, the observed number of correlated components was higher than expected by chance: there were 20 correlated components in sample C collected during RT and 16 correlated components in sample D collected immediately after the end of RT

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Summary

Introduction

Radiotherapy (RT), either alone or in combination with other treatment modalities, is an effective treatment of patients suffering from different types of cancer which allows the delivery of a cytotoxic dose to the tumor while sparing the structure and function of critical healthy organs. In spite of very heterogeneous material, the authors identified clear differences between pre-exposure and post-exposure samples [20] Another comparative analysis of pre- and post-RT blood samples was performed on a group of larynx cancer patients treated with doses ranging from 51 to 72 Gy, which allowed detection of radiation-related changes in the serum peptidome after the end of RT [21]. Further analysis of IMRT-related effects in a group of patients suffering from head and neck cancer (head and neck squamous cell carcinoma (HNSCC)) revealed that changes in serum peptidome features were associated with intensity of acute mucosal toxicity and were affected by low-to-medium doses delivered to large volumes of normal tissues [22]. The multi-protein serum signature of response to partial body irradiation during treatment of HNSCC patients was proposed, which included up-regulation of inflammation-related factors, and down-regulation of apolipoproteins and blood coagulation-related factors [23]

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