Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

DNA Repair Capacity in Peripheral Blood Lymphocytes Predicts Efficacy of Platinum-based Chemotherapy in Patients with Gastric Cancer

  • Zhang, Yi-Yin (Department of Medicine Oncology, the First Affiliated Hospital, Anhui Medical University) ;
  • Gu, Kang-Sheng (Department of Medicine Oncology, the First Affiliated Hospital, Anhui Medical University)
  • Published : 2013.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: To investigate the correlation between ERCC1 expression levels in tumor tissue and peripheral blood lymphocytes (PBL) from patients with gastric cancer and assess the relationship between PBL DNA repair rate (DRR) and the efficacy of platinum chemotherapy. Methods: A total of 53 patients with gastric cancer receiving surgery and 20 controls were studied. ERCC1 protein expression in tumour tissue and PBL were determined by immunohistochemical staining. The PBL DRRs of 47 advanced patients and 20 controls were estimated by comet assay. Results: The positive expression rates of ERCC1 were 67. 9%, 56. 6% and 10.0% in tumour tissues, PBLs of gastric cancer patients, and PBLs of the control group. PBL ERCC1 expression correlated with that in tissue (${\chi}^2$=15. 463, p=0.000). Pearson contingency coefficient=0.475). DRRs of cancer patients by tail length (TL) (Z=4. 662, p=0.000) and tail moment (TM) (Z=3. 827, p=0.000) were significantly lower than that of control group. When TL was applied as an indicator, the correlation between DRR and chemotherapy efficacy was significant (Spearman rank correlation r=0.327, p=0.032). Patients with low levels of DRR in PBL presented better short-term efficacy of chemotherapy than those with high levels of DRR. Conclusions: The ERCC1 expression in PBLs may indirectly reflect ERCC1 expression in gastric cancer tissues. Compared with non-cancer populations, patients with gastric cancer may have lower DNA repair capacity. DRR in PBL may predict the short-term efficacy of platinum-based chemotherapy for patients with advanced gastric cancer.

Keywords

References

  1. Darcy KM, Tian C, Reed E (2007). A Gynecologic Oncology Group study of platinum-DNA adducts and excision repair cross-complementation group 1 expression in optimal, stage III epithelial ovarian cancer treated with platinum-taxane chemotherapy. Cancer Res, 67, 4474-81. https://doi.org/10.1158/0008-5472.CAN-06-4076
  2. Kaspers CIL, Pieters R, Zantwijk CHV, et al (1991). In vitro drug sensitivity of normal peripheral blood lymphocyte and childhood leakemic from bone marrow and peripheral blood. Br J Cancer, 64, 469-74. https://doi.org/10.1038/bjc.1991.333
  3. Lou J, He J, Zheng W, et al (2007). Investigating the genetic instability in the peripheral lymphocytes of 36 untreated lung cancer patients with comet assay and micronucleus assay. Mutat Res, 617, 104-10. https://doi.org/10.1016/j.mrfmmm.2007.01.004
  4. Matsubara J, Nishina T, Yamada Y, et al (2008). Impacts of excision repair c ross-complementing gene-1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric Cancer. Br J Cancer, 98, 832-9. https://doi.org/10.1038/sj.bjc.6604211
  5. McGurk CJ, Cummings M, Koberle B, et al (2006). Regulation of DNA repair gene expression in human cancer cell lines. J Cell Biochem, 97, 1121-36. https://doi.org/10.1002/jcb.20711
  6. Metzger R, Leichman CG, Danenberg KD, et al (1998). ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol, 16, 309-17. https://doi.org/10.1200/JCO.1998.16.1.309
  7. Niedernhofer LJ, Odijk H, Budzowska M, et al (2004). The structure specific endonuclease ERCC1 XPF is required to resolve DNA interstrand cross-link induced double strand breaks. Mol Cell Biol, 24, 5776-87. https://doi.org/10.1128/MCB.24.13.5776-5787.2004
  8. Nadin SB, Vargas-Roig LM, Drago G, et al (2006). DNA damage and repair in peripheral blood lymphocytes from healthy individuals and cancer patients: a pilot study on the implications in the clinical response to chemotherapy. Cancer Lett, 239, 84-97. https://doi.org/10.1016/j.canlet.2005.07.025
  9. Ozkan M, Akbudak IH, Deniz K, et al (2010). Prognostic value of excision repair cross-complementing gene 1 expression for cisplatin-based chemotherapy in advanced gastric cancer. Asian Pac J Cancer Prev, 11, 181-5.
  10. Rabik CA, Dolan ME (2007). Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev, 33, 9-23 https://doi.org/10.1016/j.ctrv.2006.09.006
  11. Schena M, Guarrera S, Buffoni L, et al (2012). DNA repair gene expression level in peripheral blood and tumour tissue from non-small cell lung cancer and head and neck squamous cell cancer patients. DNA Repair (Amst), 11, 374-80. https://doi.org/10.1016/j.dnarep.2012.01.003
  12. Schmezer P, Rajaee BN, Risch A, et al (2001). Rapid screening assay for mutagen sensitivity and DNA repair capacity in human peripheral blood lymphocytes. Mutagenesis, 16, 25-30. https://doi.org/10.1093/mutage/16.1.25
  13. Singh NP, McCoy MT, Tice RR, et al (1988). A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res, 175, 184-91. https://doi.org/10.1016/0014-4827(88)90265-0
  14. Slyskova J, Naccarati A, Pardini B, et al (2012). Differences in nucleotide excision repair capacity between newly diagnosed colorectal cancer patients and healthy controls. Mutagenesis, 27, 519-22 https://doi.org/10.1093/mutage/ges021
  15. Wachters FM, Wong LS, Timens W, et al (2005). ERCC1, hRad51, and BRCA1 protein expression in relation to tumor response and survival of stage III/IV NSCLC patients treated with chemotherapy. Lung Cancer, 50, 211-9. https://doi.org/10.1016/j.lungcan.2005.06.013
  16. Wang LE, Yin M, Dong Q, et al (2011). DNA repair capacity in peripheral lymphocytes predicts survival of patients with non-small-cell lung cancer treated with first-line platinumbased chemotherapy. J Clin Oncol, 29, 4121-8. https://doi.org/10.1200/JCO.2010.34.3616
  17. Wang S, Wu X, Chen Y, et al (2012). Prognostic and predictive role of JWA and XRCC1 expressions in gastric cancer. Clin Cancer Res, 18, 2987-96. https://doi.org/10.1158/1078-0432.CCR-11-2863
  18. Wei Z, Lifen J, Jiliang H, et al (2005). Detecting DNA repair capacity of peripheral lymphocytes from cancer patients with UVC challenge test and bleomycin challenge test. Mutagenesis, 20, 271-7. https://doi.org/10.1093/mutage/gei037
  19. Yang M, Kim WH, Choi Y, et al (2006). Effects of ERCC1 expression in peripheral blood on the risk of head and neck cancer. Eur J Cancer Prev, 15, 269-73. https://doi.org/10.1097/01.cej.0000195709.79696.0c
  20. Yin M, Yan J, Martinez-Balibrea E, et al (2011). ERCC1 and ERCC2 polymorphisms predict clinical outcomes of oxaliplatin-based chemotherapies in gastric and colorectal cancer: a systemic review and meta-analysis. Clin Cancer Res, 17, 1632-40. https://doi.org/10.1158/1078-0432.CCR-10-2169
  21. Zhang GB, Chen J, Wang LR, et al (2012). RRM1 and ERCC1 expression in peripheral blood versus tumor tissue in gemcitabine/carboplatin-treated advanced non-small cell lung cancer. Cancer Chemother Pharmacol, 69, 1277-87. https://doi.org/10.1007/s00280-012-1834-x
  22. Zheng W, He JL, Jin LF, et al (2005). Assessment of human DNA repair (NER) capacity with DNA repair rate (DRR) by comet assay. Biomed Environ Sci, 18, 117-23.

Cited by

  1. ERCC1 as a Biological Marker Guiding Management in Malignant Pleural Mesothelioma vol.15, pp.10, 2014, https://doi.org/10.7314/APJCP.2014.15.10.4117
  2. Clinical Study on Carboplatin for Treating Pediatric Patients with Wilms Tumors vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7277