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 |
Appears in Collections: | Staff Publications Elements |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
10_1186_s12885-018-5005-2.pdf | 1.57 MB | Adobe PDF | OPEN | None | View/Download |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.