Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer
Open Access
- 22 March 2020
- Vol. 12 (3), 753
- https://doi.org/10.3390/cancers12030753
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.This publication has 73 references indexed in Scilit:
- The Cancer Genome Atlas Pan-Cancer analysis projectNature Genetics, 2013
- Pan-cancer patterns of somatic copy number alterationNature Genetics, 2013
- The PI3K/Akt/mTOR Pathway Is Implicated in the Premature Senescence of Primary Human Endothelial Cells Exposed to Chronic RadiationPLOS ONE, 2013
- Association of single nucleotide polymorphisms in the genes ATM, GSTP1, SOD2, TGFB1, XPD and XRCC1 with risk of severe erythema after breast conserving radiotherapyRadiation Oncology, 2012
- Hypoxia-induced Acidosis Uncouples the STIM-Orai Calcium Signaling Complex*Journal of Biological Chemistry, 2011
- Polymorphisms of Homologous Recombination Genes and Clinical Outcomes of Non-Small Cell Lung Cancer Patients Treated with Definitive RadiotherapyPLOS ONE, 2011
- Variance decomposition of protein profiles from antibody arrays using a longitudinal twin modelProteome Science, 2011
- Molecular physiology and genetics of Na+-independent SLC4 anion exchangersJournal of Experimental Biology, 2009
- Vascular permeability, vascular hyperpermeability and angiogenesisAngiogenesis, 2008
- KEGG: Kyoto Encyclopedia of Genes and GenomesNucleic Acids Research, 2000