Quantitative proteomic analysis reveals AK2 as potential biomarker for late normal tissue radiotoxicity

Area of Science:

• Proteomics
• Radiation Oncology
• Biomarker Discovery

Background:

• Predictive biomarkers for late normal tissue toxicity in radiotherapy are crucial for personalized treatment and optimizing clinical benefit.
• While radiogenomic studies are abundant, proteomics approaches for predicting radiotherapy toxicity remain underdeveloped.
• This study addresses the need for advanced proteomic methods to identify biomarkers for radiation-induced normal tissue damage.

Purpose of the Study:

• To identify protein expression differences in T lymphocytes from patients with varying degrees of radiation-induced breast fibrosis.
• To investigate the role of oxidative stress and NADPH oxidases (NOXs) in the development of late radiotherapy toxicity.
• To discover novel biomarkers for predicting patient response to radiotherapy.

Main Methods:

• Utilized isobaric tags for relative and absolute quantitation (iTRAQ) proteomics to analyze ex-vivo irradiated T lymphocytes.
• Compared protein expression in patients with grade ≥2 radiation-induced breast fibrosis (bf+) and grade <2 bf+.
• Validated candidate protein expression using immunoblotting and assessed reactive oxygen species (ROS) production and NOX expression.

Main Results:

• Identified 23 candidate proteins out of 1979 quantified proteins.
• Confirmed overexpression of Adenylate Kinase 2 (AK2) in irradiated T lymphocytes from patients with grade ≥2 bf+.
• Observed increased ROS and superoxide anion levels post-irradiation, with significantly higher NOX4 mRNA levels in the grade ≥2 bf+ group.

Conclusions:

• Adenylate Kinase 2 (AK2) is identified as a potential biomarker for radiosensitivity and predicting radiation-induced breast fibrosis.
• The proteomic approach underscores the significant role of oxidative stress in late radiation toxicity.
• Further research into NOXs and superoxide ion metabolism is warranted for understanding and managing radiotherapy-induced toxicity.