A comprehensive comparison between short-term effect of Boost versus Radical dose of Intraoperative electron Radiotherapy(IOeRT) in breast cancer tumor bed using transcriptomics and proteomics approaches

Introduction Intra-operative electron Radiation Therapy (IOeRT) as a partial-breast single high dose radiotherapy, leads to decrease the local recurrence through tumor bed modification. This study designed to investigate short-term effect of the dose- dependent and -independent molecular mechanisms and biological pathway of tumor bed modification induced by IOeRT using transcriptomics and proteomics profiling. Methods Six random selected breast cancer patients entered into our study and all patients by referee to their pathological report were treated by doses of 12Gy as a Boost dose and 21Gy as a Radical dose and the samples were categorized into three groups. High-throughput technologies such as mRNA sequencing (RNA-Seq) and Isobaric Tag for Relative and Absolute Quantitation (iTRAQ) were performed to study the transcriptome and proteome profile of the tumor bed. Results Using mRNA-sequencing, ~6Gb clean data (20 Million Reads, 150bp) per individual samples were generated from the patient samples. Moreover, using iTRAQ for proteome quantification, in total 5860 proteins were identified (FDR <0.01). Discussion Functional annotation of differentially expressed genes and proteins indicated that the most of beneficial biological pathways for local and systemic response to short-term IOeRT effects have induced in tumor bed, independently to the Boost versus Radical dosage and increased radiation intensity used in Radical dosage seems has not provided more remarkable biological changes in the respect of molecular pathways. Therefore, more molecular profiling by long-term follow-up of breast tumor recurrences will provide deep insight to biological mechanisms of recurrence besides of these short-term effects. 

Keywords:

Intraoperative electron Radiation Therapy , mRNA sequencing , Isobaric Tag for Relative and Absolute Quantitation (iTRAQ)