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Article

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

1
Affinity Proteomics, Science for Life Laboratory, Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH – Royal Institute of Technology, Tomtebodavägen 23, 171 65 Stockholm, Sweden
2
Yale Cancer Center, Department of Internal Medicine, Yale University School of Medicine, 06511 New Haven, CT, USA
3
Department of Data Science and Engineering, Silesian University of Technology, 44-100 Gliwice, Poland
4
Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176, Stockholm, Sweden
5
Reconstructive Plastic Surgery, Karolinska University Hospital, 17176 Stockholm, Sweden
6
Department of Clinical Science, Intervention and Technology, Division of ENT Diseases, Karolinska Institutet, 14186 Stockholm, Sweden
7
Department of Oral and Maxillofacial Surgery, Karolinska University Hospital, 17176, Stockholm, Sweden
8
Centre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner-Gren Institute Stockholm University, 10691 Stockholm, Sweden
9
Department of Radiotherapy, Karolinska University Hospital, 17176 Stockholm, Sweden
10
University of Caen Normandy, Department of medicine, Cimap-Laria, Advanced Resource Center for HADrontherapy in Europe (ARCHADE), 14076 Caen, France
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(3), 753; https://doi.org/10.3390/cancers12030753
Received: 27 February 2020 / Revised: 13 March 2020 / Accepted: 16 March 2020 / Published: 22 March 2020
(This article belongs to the Special Issue Plasma Proteins and Cancer)
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. View Full-Text
Keywords: radiosensitivity; prediction; plasma proteins; radiotherapy; breast cancer; head-and-neck cancer; skin reaction; biomarker; mandibular osteoradionecrosis; ionizing radiation; radiotherapy side effects; personalized radiotherapy  radiosensitivity; prediction; plasma proteins; radiotherapy; breast cancer; head-and-neck cancer; skin reaction; biomarker; mandibular osteoradionecrosis; ionizing radiation; radiotherapy side effects; personalized radiotherapy 
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MDPI and ACS Style

Drobin, K.; Marczyk, M.; Halle, M.; Danielsson, D.; Papiez, A.; Sangsuwan, T.; Bendes, A.; Hong, M.-G.; Qundos, U.; Harms-Ringdahl, M.; Wersäll, P.; Polanska, J.; Schwenk, J.M.; Haghdoost, S. Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer. Cancers 2020, 12, 753. https://doi.org/10.3390/cancers12030753

AMA Style

Drobin K, Marczyk M, Halle M, Danielsson D, Papiez A, Sangsuwan T, Bendes A, Hong M-G, Qundos U, Harms-Ringdahl M, Wersäll P, Polanska J, Schwenk JM, Haghdoost S. Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer. Cancers. 2020; 12(3):753. https://doi.org/10.3390/cancers12030753

Chicago/Turabian Style

Drobin, Kimi, Michal Marczyk, Martin Halle, Daniel Danielsson, Anna Papiez, Traimate Sangsuwan, Annika Bendes, Mun-Gwan Hong, Ulrika Qundos, Mats Harms-Ringdahl, Peter Wersäll, Joanna Polanska, Jochen M. Schwenk, and Siamak Haghdoost. 2020. "Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer" Cancers 12, no. 3: 753. https://doi.org/10.3390/cancers12030753

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