Abstract
Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival, may appear during or long time after finishing radiotherapy and depend on the patient’s radiosensitivity. Currently, there is no assay available that can reliably predict the individual’s response to radiotherapy. We profiled two study sets from breast (n = 29) and head-and-neck cancer patients (n = 74) that included radiosensitive patients and matched radioresistant controls.. We studied 55 single nucleotide polymorphisms (SNPs) in 33 genes by DNA genotyping and 130 circulating proteins by affinity-based plasma proteomics. In both study sets, we discovered several plasma proteins with the predictive power to find radiosensitive patients (adjusted p < 0.05) and validated the two most predictive proteins (THPO and STIM1) by sandwich immunoassays. By integrating genotypic and proteomic data into an analysis model, it was found that the proteins CHIT1, PDGFB, PNKD, RP2, SERPINC1, SLC4A, STIM1, and THPO, as well as the VEGFA gene variant rs69947, predicted radiosensitivity of our breast cancer (AUC = 0.76) and head-and-neck cancer (AUC = 0.89) patients. In conclusion, circulating proteins and a SNP variant of VEGFA suggest that processes such as vascular growth capacity, immune response, DNA repair and oxidative stress/hypoxia may be involved in an individual’s risk of experiencing radiation-induced toxicity.
Highlights
Beside its therapeutic properties against cancer, radiotherapy inevitably involves exposure of normal tissues where late as well as acute adverse effects are dose-limiting factors for the treatment.Numerous attempts have been made to develop an assay that can be used for identifying radiotherapy (RT) patients who will develop severe adverse healthy tissue reactions [1,2,3]
A list of predicative candidate proteins was generated mainly based on our previous study [6], where intracellular protein profiles from leukocytes of extremely (RTOG 3/4) and normally radiosensitive (RTOG 0/1) breast cancer patients were established using isotope-coded protein labeling (ICPL)
We included other possible protein candidates that were identified using network analysis tools and from literature data of related research on in vitro irradiation of cells [16,18,19,20], as well as proteins associated with DNA repair and signaling
Summary
Beside its therapeutic properties against cancer, radiotherapy inevitably involves exposure of normal tissues where late as well as acute adverse effects are dose-limiting factors for the treatment.Numerous attempts have been made to develop an assay that can be used for identifying radiotherapy (RT) patients who will develop severe adverse healthy tissue reactions [1,2,3]. The identification of patients at high risk of developing severe side effects is important as it would allow clinicians to consider a change to the standard available RT protocol and/or combine it with other therapeutic alternatives that reduce the risk of damage to healthy tissues. This is a interesting concept for pediatric cancer patients with long-time survival as well as cancer types where wider surgical margins may be an option to RT, such as breast cancer (BC) and head-and-neck cancer (HNC). There is currently no standard test available that can reliably predict radiosensitivity (RS) on an individual level
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
