Table 1.
(a) Study characteristics of included records concerning repair foci. (b) Study characteristics of included records containing proteins other than repair foci.
| (a) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Author, Date | Title | Study Design | Sample-Size | Methods Used | Statistical Method | Repair Foci | Viability | Cell System |
| Vasireddy, 2010 [25] | H2AX phosphorylation screen of cells from radiosensitive cancer patients reveals a novel DNA double-strand break repair cellular phenotype | Cohort | 29 | IF | nr | γH2AX | (RTOG) | lymphoblastoid cell lines (LCLs) |
| Bourton, 2011 [26] | Prolonged expression of the γ-H2AX DNA repair biomarker correlates with excess acute and chronic toxicity from radiotherapy treatment | Cohort | 30 | FACS | unpaired t-test | γH2AX | (RTOG) | lymphocytes |
| Goutham, 2012 [33] | DNA double-strand break analysis by γ-H2AX foci: a useful method for determining the overreactors to radiation-induced acute reactions among head-and-neck cancer patients | Cohort | 54 | IF | nr | γH2AX | (RTOG) | lymphocytes |
| Djuzenova, 2013 [32] | Radiosensitivity in breast cancer assessed by the histone γ-H2AX and 53BP1 foci | Cohort | 69 | IF | Student’s t-test or one way ANOVA | γH2AX, 53BP1 | (RTOG) | PBMCs |
| Mumbrekar, 2013 [27] | Influence of double-strand break repair on radiation therapy-induced acute skin reactions in breast cancer patients | Cohort | 118 | IF | t test, ANOVA followed by Tukey multiple comparison tests and Pearson correlation test | γH2AX | (RTOG) | lymphocytes |
| Oorschot, 2013 [24] | Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity | Cohort | 61 | IF | Continuous variables: Shapiro-Wilk test, normal distributed data: unpaired Student t test, non-normal distributed data: Mann–Whitney test | γH2AX | Late toxicity using EORTC | lymphocytes |
| Granzotto, 2015 [31] | Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity | Cohort | 117 | IF | ANOVA | γH2AX, pATM | Common Terminology CTCAE, RTOG | fibroblasts |
| Pouliliou, 2015 [28] | Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities | Cohort | 89 | WB | nr | γH2AX | Common Terminology CTCAE, Trypan Blue assay | PBMCs |
| Lobachevsky, 2016 [29] | Compromised DNA repair as a basis for identification of cancer radiotherapy patients with extreme radiosensitivity | Cohort | 28 | IF | Unpaired t-test, Mann–Whitney test | γH2AX | (RTOG) | lymphocytes, hair follicles |
| Buchbinder, 2018 [30] | Application of a radiosensitivity flow assay in a patient with DNA ligase 4 deficiency | Cohort | 11 | IF | nr | γH2AX | known sensitivity LIG4-SCID | T cells |
| Vandersickel, 2010 [34] | Early Increase in Radiation-induced γH2AX Foci in a HumanKu70/80 Knockdown Cell Line Characterised by an Enhanced Radiosensitivity | model system | 1 | IF | nr | γH2AX | known sensitivity Ku70i | LVTHM cells synchronised in the G0–G1 phase, Ku70i cells synchronised in the G0–G1 phase |
| Martin, 2011 [36] | Assessing ’radiosensitivity’ with kinetic profiles of γ-H2AX, 53BP1 and BRCA1 foci | model system | 15 | IF | unpaired t test | γH2AX, 53BP1 | clonogenic survival | LCL |
| Martin, 2014 [35] | Homozygous mutation of MTPAP causes cellular radiosensitivity and persistent DNA double-strand breaks | model system | 4 | IF | Student’s t-test | γH2AX | clonogenic survival | LCL |
| Minafra, 2015 [37] | Gene Expression Profiling of MCF10A Breast Epithelial Cells Exposed to IOERT | model system | 1 | IF | nr | γH2AX | clonogenic survival | MCF10A |
| Miyake, 2019 [38] | DNA Damage Response After Ionizing Radiation Exposure in Skin Keratinocytes Derived from Human-Induced Pluripotent Stem Cells | model system | 1 | IF | Student’s t test (1-tailed) | γH2AX, 53BP1 | Cell survival WST-8 assay; TUNEL assay | Normal human skin fibroblast NB1RGB, iPSCs NB1RGB C2, NB1RGB KCs 1stP, NB1RGB KCs 2ndP, NB1RGB KCs 3rdP |
| Nguyen, 2019 [39] | Human CCR6+ Th17 Lymphocytes Are Highly Sensitive to Radiation-Induced Senescence and Are a Potential Target for Prevention of Radiation-Induced Toxicity | model system | 32 | IF | two-tailed Mann–Whitney U-test, Kruskal–Wallis test | γH2AX | Annexin V-FITC; Senescence-associated β-Galactosidase | Treg, CCR6+Th17, CCR6negTh |
| (b) | ||||||||
| Author, Date | Title | Study Design | Sample-Size | Methods Used | Statistical Method | Results (Protein Name) | Viability | Cell System |
| Braicu, 2014 [40] | Role of serum VEGFA, TIMP2, MMP2, and MMP9 in Monitoring Response to Adjuvant Radiochemotherapy in Patients with Primary Cervical Cancer – Results of a Companion Protocol of the Randomised NOGGO-AGO Phase III Clinical Trial | Cohort | 72 | ELISA | Fisher’s exact test | VEGFA, TIMP2, MMP2, MMP9 | overall survival | Serum |
| Rodriguez-Gil, 2014 [41] | Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in Patients with Breast Cancer | Cohort | 159 | ELISA | two-sided Student’s t-test | C-reactive protein (CRP) | EASR | plasma |
| Skiöld, 2014 [42] | Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients | Cohort | 17 | LC-MS/MS | Student’s t-test | 8-oxo-dG, BLVRB, PRDX2, SOD1, CA1, PARK7, SH3BGRL3 | RTOG | blood/leukocytes (RTOG 0), blood/leukocytes (RTOG 4) |
| Yu, 2018 [43] | Cofilin-2 Acts as a Marker for Predicting Radiotherapy Response and Is a Potential Therapeutic Target in Nasopharyngeal Carcinoma | Cohort | 70 | ELISA | Wilcoxon rank-sum test, t test or one-way analysis of variance (ANOVA) | Cofilin-2 | Patients were divided into radiosensitivity and radio-resistance groups according to therapeutic effects | Serum |
| Lacombe, 2019 [44] | Quantitative proteomic analysis reveals AK2 as potential biomarker for late normal tissue radiotoxicity | Cohort | 5 | WB | Mann–Whitney test | adenylate kinase 2 (AK2), annexin A1 (ANXA1), isocitrate dehydrogenase 2 (IDH2), HSPA8, Nox4 | RILA | T lymphocytes (Grade > 2 breast fibrosis+), T lymphocytes (Grade < 2 breast fibrosis+) |
| Cao, 2011 [45] | Different radiosensitivity of CD4+CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro | model system | 5 | FACS, Luminex | Wilcoxon’s signed rank test | Caspase 3, Bax, IL-1 Beta, IL-2, IL-4, IL-6, IL-10, Interferon Gamma, TNF alpha | Annexin V-FITC | CD4+CD25+ regulatory T cells and effector T cells |
| Park, 2012 [46] | Radio-sensitivities and angiogenic signaling pathways of irradiated normal endothelial cells derived from diverse human organs | model system | 1 | ELISA | Student’s t-test | angiostatin | clonogenic survival | HHSEC, HDMEC |
| Fekete, 2015 [47] | Effect of High-Dose Irradiation on Human Bone-Marrow-Derived Mesenchymal Stromal Cells | model system | nr | Luminex | unpaired, two sided Student’s t-test | PDGF-AA, PDGF-AB/BB, GRO, IL-6, VEGF | CyQUANT Cell Proliferation Assay, Trypan blue staining, colony formation | MSCs |
| Minafra, 2015 [37] | Gene Expression Profiling of MCF10A Breast Epithelial Cells Exposed to IOERT | model system | 1 | WB | nr | PARP, FAS, Pro-Caspase 8, PLK1, P53, p-EGFR, EGFR, c-MYC, | clonogenic survival | MCF10A cell line |
| Nishad, 2015 [48] | Dynamic changes in the proteome of human peripheral blood mononuclear cells with low dose ionizing radiation Radiotherapy-Induced Early Adverse Skin Reactions in | model system | 8 | 2DE-MS, WB | Student’s t-test | GRP78, HSP90, PDIA3, PRDX6 | trypan blue, PI Staining, alkaline comet assay | PBMCs |
| Shimura, 2015 [49] | Nuclear accumulation of cyclin D1 following long-term fractionated exposures to low-dose ionizing radiation in normal human diploid cells | model system | 1 | WB | Student’s t-test | cyclin D1 | cell growth assay | WI-38 (detergent insoluble fraction) |
| Yim, 2017 [50] | Phosphoprotein profiles of candidate markers for early cellular responses to low-dose γ-radiation in normal human fibroblast cells | model system | 1 | WB, antibody microarray | Student’s t-test | Phospho-Gab2 (Tyr643), Phospho-P95/NBS (Ser343), Phospho-BTK (Tyr550), Phospho-Elk1 (Ser383), Phospho-ETK (Tyr40), Phospho-CaMK4 (Thr196/200), Phospho-MEK1 (Thr298), Phospho-PLCG1 (Tyr1253), Phospho-IRS-1 (Ser612), Phospho-TFII-I (Tyr248), Phospho-IKK-alpha/beta (Ser176/177), Phospho-MEK1 (Thr286), Phospho-Pyk2 (Tyr580), Phospho-Keratin 8 (Ser431), Phospho-ERK3 (Ser189), Phospho-Chk1 (Ser296), Phospho-CBL (Tyr700), Phospho-BTK (Tyr550), Phospho-LIMK1/2 (Thr508/505), p-BTK(Tyr550)/BTK, p-Gab2(Tyr643)/Gab2, p-BTK(Tyr550)/BTK, p-Gab2(Tyr643)/Gab2, | MTT | MRC5, NHDF |
| Miyake, 2019 [38] | DNA Damage Response After Ionizing Radiation Exposure in Skin Keratinocytes Derived from Human-Induced Pluripotent Stem Cells | model system | 1 | IF | Student’s t test (1-tailed) | p16 | Cell survival WST-8 assay, TUNEL assay | Skin keratinocytes were derived from iPSCs |
| Nguyen, 2019 [39] | Human CCR6+Th17 lymphocytes are highly sensitive to radiation-induced senescence and are a potential target for prevention of radiation-induced toxicity | model system | 32 | IF, Luminex | two-tailed Mann–Whitney U-test, Kruskal–Wallis test | Caspase 3, p16Ink4a, p21Cdkn1a, IL-1 Beta, VEGF-A, IL-8, H2A.J | Annexin V-FITC, Senescence-associated β-Galactosidase | CCR6+Th17 lymphocytes |
| Moertl, 2020 [51] | Radiation Exposure of Peripheral Mononuclear Blood Cells Alters the Composition and Function of Secreted Extracellular Vesicles | model system | 5 | LC-MS/MS | two-sided Student’s t-test | hemopexin (HPX), syntaxin-binding protein 3 (STXBP3), proteasome subunit alpha type-6 (PSMA6) | sub-G1 fraction, Caspase 3 activity | PBMC-derived EVs |
Abbreviations: (a) Criteria for adverse events (CTCAE), European organisation for research and treatment of cancer (EORTC), Fluorescence-activated cell sorting (FACS), Immunofluorescence (IF), not reported (nr), Peripheral blood mononuclear cell (PBMC), Radiation therapy oncology group (RTOG), Western Blot WB). (b) Two-dimensional gel electrophoresis (2-DE), Enzyme-linked immunosorbent assay (ELISA), Immunofluorescence (IF), Liquid chromatography (LC), Mass spectrometry (MS), not reported (nr), radiation-induced lymphocyte apoptosis (RILA), Radiation therapy oncology group (RTOG), Western blot (WB).