Please use this identifier to cite or link to this item: https://doi.org/10.1186/s12885-018-5005-2
Title: Intra-patient and inter-patient comparisons of DNA damage response biomarkers in Nasopharynx Cancer (NPC): Analysis of NCC0901 randomised controlled trial of induction chemotherapy in locally advanced NPC
Authors: Chua K.L.M. 
Yeo E.L.L. 
Shihabudeen W.A.
Tan S.H. 
Shwe T.T.
Ong E.H.W.
Lam P.Y.P. 
Soo K.C. 
Soong Y.L. 
Fong K.W. 
Tan T.W.K. 
Wee J.T.S. 
Chua M.L.K. 
Keywords: biological marker
carboplatin
gemcitabine
histone H2AX
paclitaxel
antineoplastic agent
biological marker
histone
adult
advanced cancer
age
apoptosis
Article
cancer chemotherapy
cancer radiotherapy
case control study
CD4+ T lymphocyte
CD8+ T lymphocyte
cell assay
cohort analysis
comparative study
controlled study
DNA damage response
DNA repair
ex vivo study
exploratory research
female
human
human cell
induction chemotherapy
lymphocyte
major clinical study
male
middle aged
nasopharynx cancer
phase 2 clinical trial (topic)
phase 3 clinical trial (topic)
radiation dose
radiation injury
randomized controlled trial (topic)
retrospective study
xerostomia
aged
cancer staging
clinical trial
DNA damage
drug effect
genetics
induction chemotherapy
ionizing radiation
metabolism
nasopharynx tumor
pathology
phase 2 clinical trial
phase 3 clinical trial
radiation response
young adult
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Apoptosis
Biomarkers
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
DNA Damage
DNA Repair
Female
Histones
Humans
Induction Chemotherapy
Male
Middle Aged
Nasopharyngeal Neoplasms
Neoplasm Staging
Radiation, Ionizing
Young Adult
Issue Date: 2018
Citation: Chua K.L.M., Yeo E.L.L., Shihabudeen W.A., Tan S.H., Shwe T.T., Ong E.H.W., Lam P.Y.P., Soo K.C., Soong Y.L., Fong K.W., Tan T.W.K., Wee J.T.S., Chua M.L.K. (2018). Intra-patient and inter-patient comparisons of DNA damage response biomarkers in Nasopharynx Cancer (NPC): Analysis of NCC0901 randomised controlled trial of induction chemotherapy in locally advanced NPC. BMC Cancer 18 (1) : 1095. ScholarBank@NUS Repository. https://doi.org/10.1186/s12885-018-5005-2
Abstract: Background: Inter-patient heterogeneity in radiation-induced DNA damage responses is proposed to reflect intrinsic variations in tumour and normal tissue radiation sensitivity, but the prediction of phenotype by a molecular biomarker is influenced by clinical confounders and assay reproducibility. Here, we characterised the intrapatient and inter-patient heterogeneity in biomarkers of DNA damage and repair and radiation-induced apoptosis. Methods: We enrolled 85 of 172 patients with locally advanced nasopharynx cancer from a randomised controlled phase II/III trial of induction chemotherapy added to chemo-radiotherapy. G0 blood lymphocytes were harvested from these patients, and irradiated with 1, 4, and 8 Gy ex vivo. DNA damage induction (1 Gy 0.5 h) and repair (4 Gy 24 h) were assessed by duplicate ?H2AX foci assays in 50-100 cells. Duplicate FLICA assays performed at 48 h post-8 Gy were employed as surrogate of radiation-induced apoptosis; %FLICA-positive cells were quantified by flow cytometry. Results: We observed limited intrapatient variation in ?H2AX foci and %FLICA readouts; median difference of duplicate foci scores was - 0.37 (IQR = - 1.256-0.800) for 1 Gy 0.5 h and 0.09 (IQR = - 0.685-0.792) for 4 Gy 24 h; ICC of ?0.80 was observed for duplicate %FLICA0Gy and %FLICA8Gy assays of CD4+ and CD8+ T lymphocytes. As expected, we observed wide inter-patient heterogeneity in both assays that was independent of intrapatient variation and clinical covariates, with the exception of age, which was inversely correlated with %FLICAbackground-corrected (Spearman R = - 0.406, P < 0.001 [CD4+]; R = - 0.220, P = 0.04 [CD8+]). Lastly, an exploratory case-control analysis indicates increased levels of ?H2AX foci at 4 Gy 24 h in patients with severe late radiotherapy-induced xerostomia (P = 0.05). Conclusion: Here, we confirmed the technical reproducibility of DNA damage response assays for clinical implementation as biomarkers of clinical radiosensitivity in nasopharynx cancer patients. © 2018 The Author(s).
Source Title: BMC Cancer
URI: https://scholarbank.nus.edu.sg/handle/10635/175356
ISSN: 1471-2407
DOI: 10.1186/s12885-018-5005-2
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