Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer

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.

Association of Inflammation-Related Gene Polymorphisms With Susceptibility and Radiotherapy Sensitivity in Head and Neck Squamous Cell Carcinoma Patients in Northeast China

“…Drobin et al reported the correlation and possible mechanism of VEGFA rs69947 with breast cancer and HNSCC radiotherapy sensitivity. The authors proposed that this SNP may affect protein expression, which would impact biological processes such as blood vessel growth, inflammatory cell infiltration, the immune response, DNA repair, oxidative stress and hypoxia (66). These changes may underlie the differences in correlation and sensitivity among patients.…”

Objective Evaluation of Risk Factors for Radiation Dermatitis in Whole-Breast Irradiation Using the Spectrophotometric L*a*b Color-Space

“…Ideally, future objective studies in the field of RID research should also reflect patients’ genetic, epigenetic, and molecular profiles, since several promising relationships of tissue sensitivity towards radiotherapy have been described. Even though this kind of research is still in its infancy, we expect it to provide further clinically relevant insights into risk factors for radiotherapy-induced side effects [ 32 , 33 , 34 ].…”

Pan-Cancer Analysis of Radiotherapy Benefits and Immune Infiltration in Multiple Human Cancers

“…Previous studies have generated an RSS base on the intrinsic radiosensitivity in BRCA by the integration of post-radiation clonogenic survival data with gene expression data [11,[24][25][26]. To demonstrate whether immune infiltration level has predictive ability for RT outcomes, we developed a Radiosensitivity Signature (RSS) in BRCA ( Figure 5).…”

“…Each picture corresponds to a different type of cancer BRCA (B), CESC (C-F), GBM(G), HNSC (H, I), LGG (J), THCA (K-P).2.1.4. BRCA radiosensitivity signature based on immune infiltrationPrevious studies have generated an RSS base on the intrinsic radiosensitivity in BRCA by the integration of post-radiation clonogenic survival data with gene expression data[11,[24][25][26]. To…”