Partial-Body Irradiation in Patients with Prostate Cancer Treated with IMRT Has Little Effect on the Composition of Serum Proteome

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.

Keywords: IMRT; mass spectrometry; prostate cancer; radiation response; serum proteomics.

Figure 1

MALDI-based serum peptidome profiling. (A) Flow chart of the blood sample collection; (B) Average mass spectrum registered in the range of 2000 to 16,000 Da for pre-treatment samples; (C) Average differential spectrum for individual pre-treatment A and within-RT C samples; (D) Scatterplot of pair-wise comparison of differential spectrum CΔA versus differential spectrum BΔA.

Figure 2

Examples of registered peptide ions, whose abundances were affected in the serum of irradiated patients. Each boxplot shows: minimum, lower quartile, median, upper quartile, and maximum values; consecutive samples are marked A, B, C, D, and E; asterisks marked significant differences comparing to pre-treatment sample A (p < 0.05).

Figure 3

Dose-volume effect in radiation response. (A) Numbers of peptidome components in within- and post-RT samples (C, D, and E, respectively) that correlated with volume of tissue irradiated at a given dose (p < 0.05) in the all-patient group; horizontal line represents a threshold corresponding to FDR = 100%; (B) Averaged dose-volume histograms for the all-patient group (RT_1 + 2) and subgroups of patients with two different treatment plans (RT_1 and RT_2).

Figure 4

Examples of proteins, whose abundances were affected in serum of irradiated patients. (A) Proteins analyzed by LC-MS/MS; each boxplot shows: minimum, lower quartile, median, upper quartile, and maximum values; (B) Pre-RT and post-RT levels of CRP assayed in two subgroups of patients with prostate cancer (RT_1 and RT_2) and patients with HNSCC, showed are mean values ± S.D. Asterisks marked statistical significance (p < 0.05) when changes between pre-RT and within-RT or post-RT samples were analyzed (samples B, C, and D, respectively, in panel A).