Transcriptomic and proteomic approaches reveal biological basis of intraoperative radiotherapy-treated tumor bed modification in breast cancer patients: A pilot study

J Proteomics. 2020 Feb 10:212:103596. doi: 10.1016/j.jprot.2019.103596. Epub 2019 Nov 21.

Abstract

Aim: Intraoperative electron Radiotherapy, herein referred to, as IOeRT is a novel approach in breast cancer (BC) treatment. This study designed to investigate short-term molecular effects of 12Gy as Boost versus 21Gy as Radical dose of IOeRT using high throughput approaches.

Materials and methods: Six BC patients as a pilot study were treated with IOeRT following two separate strategies, including Boost and Radical doses. Approximately 100 mg of tumor bed tissue retrieved from each patient (before IOeRT,immediately, 24 h post-treatment). mRNA sequencing also Isobaric tag for relative and absolute quantitation (iTRAQ) were performed to study the transcriptome and proteome profile of IOeRT-treated tumor bed.

Results: Using NGS, ~6 Giga base (GB) clean data per individual samples were generated. Moreover, by iTRAQ for proteome quantification, in total, 1,045,410 spectrums were generated, likewise 5860 proteins were identified (FDR <0.01).

Conclusion: Functional annotation and gene ontology (GO) indicated that significant enrichment in molecular pathways on BC treatment is somehow single high dose-independent. This means that, key molecular pathways in radiotherapy (RT) are equally enriched by both Boost and Radical doses. Generally, by modification of the Radical dose, with the same effectiveness, it is possible to reduce single high dose irradiation in BC.

Keywords: Gene ontology; IOeRT; Proteomics; RNA-Seq.

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy
  • Female
  • Gene Expression Regulation, Neoplastic / radiation effects*
  • Humans
  • Intraoperative Period
  • Middle Aged
  • Pilot Projects
  • Proteome / metabolism*
  • Proteome / radiation effects
  • Radiation Dosage
  • Radiotherapy / methods*
  • Transcriptome*

Substances

  • Biomarkers, Tumor
  • Proteome