DOI QR코드

DOI QR Code

mRNA Expression and Clinical Significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in Postoperative Patients with Non-Small Cell Lung Cancer

  • Han, Yi (Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University) ;
  • Wang, Xiao-Bin (Department of Thoracic Cardiovascular Surgery, Inner Mongolia Forestry General Hospital) ;
  • Xiao, Ning (Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University) ;
  • Liu, Zhi-Dong (Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University)
  • Published : 2013.05.30

Abstract

Background: To explore mRNA expression and clinical significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 genes in tumor tissue of postoperative patients with non-small cell lung cancer (NSCLC). Materials and Methods: Sixty NSCLC patients undergoing radical operation in our hospital from Nov., 2011 to Jun., 2012 were selected. Plasmid standards of ERCC1, BRCA1, RRM1, TYMS and TUBB3 were established and standard curves were prepared by SYBR fluorescent real-time quantitative PCR analysis. Samples from tumor centers were taken to detect mRNA expression of ERCC1, BRCA1, RRM1, TYMS and TUBB3 genes in cancerous tissue during operation. The total mRNA expression quantities were compared according to different clinical characteristics. Results: The total expression quantities of 5 genotypes from high to low were ERCC1>RRM1>TUBB3>TYMS>BRCA1 in turn. By pairwise comparisons, other differences showed statistical significance (p<0.05 or p<0.01) except for TYMS and TUBB3 (p>0.05); the low expression rates from high to low were ERCC1>TYMS>TUBB3>TUBB3>RRM1>BRCA1 in turn. The expression quantities of BRCA1, RRM1 and TYMS in males, smokers and patients without adenocarcinoma were all significantly higher than that in females, non-smokers and patients with adenocarcinoma, and significant differences were present (p<0.05 or p<0.01). In terms of pathological staging, the expression quantities of BRCA1, RRM1 and TYMS in phases IIa~IIb and IIIa~IIIb had a tendency to be greater than in phases I and IV. Conclusions: Resistance to chemotherapy and sensitivity to targeted therapy differ among patients with NSCLC. Differences in gene expression in different individuals were also revealed. Only according to personalized detection results can individualized therapeutic regimens be worked out, which is a new direction for oncotherapy.

Keywords

References

  1. Bartolucci R, Wei J, Sanchez JJ, et al (2009). XPG mRNA expression levels modulate prognosis in resected non-smallcell lung cancer in conjunction with BRCA1 and ERCC1 expression. Clin Lung Cancer, 10, 47-52. https://doi.org/10.3816/CLC.2009.n.007
  2. Cobo M, Isla D, Massuti B, et al (2007). Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol, 25, 2747-54. https://doi.org/10.1200/JCO.2006.09.7915
  3. Dimoudis S, Korantzis I, Pectasides D, et al (2012). Expression of DNA repair and replication genes in non-small cell lung cancer (NSCLC): a role for thymidylate synthetase (TYMS). BMC Cancer, 12, 342. https://doi.org/10.1186/1471-2407-12-342
  4. Gautschi O, Mack PC, Davies AM, et al (2008). Pharmacogenomic approaches to individualizing chemotherapy for non-smallcell lung cancer: current status and new directions. Clin Lung Cancer, 9, S129-38. https://doi.org/10.3816/CLC.2008.s.019
  5. Hubner RA, Riley RD, Billingham LJ, et al (2011). Excision repair cross-complementation group 1 (ERCC1) status and lung cancer outcomes: a meta-analysis of published studies and recommendations. PLoS One, 6, e25164. https://doi.org/10.1371/journal.pone.0025164
  6. Jazieh AR, Bamefleh H, Demirkazik A, et al (2010). Modification and implementation of NCCN guidelines on non-small cell lung cancer in the Middle East and North Africa region. J Natl Compr Canc Netw, 8, S16-21.
  7. Koh Y, Jang B, Han SW, et al (2010). Expression of class III beta-tubulin correlates with unfavorable survival outcome in patients with resected non-small cell lung cancer. J Thorac Oncol, 5, 320-5. https://doi.org/10.1097/JTO.0b013e3181ce684f
  8. Lee KH, Min HS, Han SW, et al (2008). ERCC1 expression by immunohistochemistry and EGFR mutations in resected non-small cell lung cancer. Lung Cancer, 60, 401-7. https://doi.org/10.1016/j.lungcan.2007.10.014
  9. Leng XF, Chen MW, ssXian L, et al (2012). Combined analysis of mRNA expression of ERCC1, BAG-1, BRCA1, RRM1 and TUBB3 to predict prognosis in patients with non-small cell lung cancer who received adjuvant chemotherapy. J Exp Clin Cancer Res, 31, 25. https://doi.org/10.1186/1756-9966-31-25
  10. Li XD, Han JC, Zhang YJ, et al (2013). Common variations of DNA repair genes are associated with response to platinumbased chemotherapy in NSCLCs. Asian Pac J Cancer Prev, 14, 145-8. https://doi.org/10.7314/APJCP.2013.14.1.145
  11. Li Y, Huang XE, Jin GF, et al (2011). Lack of any relationship between chemotherapy toxicity in non-small cell lung cancer cases and polymorphisms in XRCC1 codon 399 or XPD codon 751. Asian Pac J Cancer Prev, 12, 739-42.
  12. Maus MK, Mack PC, Astrow SH, et al (2013). Histology-Related Associations of ERCC1, RRM1, and TS Biomarkers in Patients with Non-Small-Cell Lung Cancer: Implications for Therapy. J Thorac Oncol, 8, 582-6.
  13. Pesta M, Kulda V, Fiala O, et al (2012). Prognostic significance of ERCC1, RRM1 and BRCA1 in surgically-treated patients with non-small cell lung cancer. Anticancer Res, 32, 5003-10.
  14. Santos ES, Blaya M, Raez LE (2009). Gene expression profiling and non-small-cell lung cancer: where are we now? Clin Lung Cancer, 10, 168-73. https://doi.org/10.3816/CLC.2009.n.023
  15. Vilmar A, Sorensen JB (2009). Excision repair crosscomplementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature. Lung Cancer, 64, 131-9. https://doi.org/10.1016/j.lungcan.2008.08.006
  16. Vilmar AC, Santoni-Rugiu E, Sorensen JB (2010). ERCC1 and histopathology in advanced NSCLC patients randomized in a large multicenter phase III trial. Ann Oncol, 21, 1817-24. https://doi.org/10.1093/annonc/mdq053
  17. Zhang ZY, Tian X, Wu R, et al (2012). Predictive role of ERCC1 and XPD genetic polymorphisms in survival of Chinese non-small cell lung cancer patients receiving chemotherapy. Asian Pac J Cancer Prev, 13, 2583-6. https://doi.org/10.7314/APJCP.2012.13.6.2583

Cited by

  1. Analysis of ICU Treatment on Resection of Giant Tumors in the Mediastinum of the Thoracic Cavity vol.14, pp.6, 2013, https://doi.org/10.7314/APJCP.2013.14.6.3843
  2. Serum CEA Level Change and Its Significance Before and after Gefitinib Therapy on Patients with Advanced Non-small Cell Lung Cancer vol.14, pp.7, 2013, https://doi.org/10.7314/APJCP.2013.14.7.4205
  3. Effect and mechanism of Src tyrosine kinase inhibitor sunitinib on the drug-resistance reversal of human A549/DDP cisplatin-resistant lung cancer cell line vol.10, pp.4, 2014, https://doi.org/10.3892/mmr.2014.2440
  4. No Association between BRCA1 Immunohistochemical Expression and Tumor Grade, Stage or Overall Survival in Platinum-Treated Epithelial Ovarian Cancer Patients vol.15, pp.10, 2014, https://doi.org/10.7314/APJCP.2014.15.10.4275
  5. ERCC1 and BRCA1 mRNA expressions are associated with clinical outcome of non-small cell lung cancer treated with platinum-based chemotherapy vol.35, pp.5, 2014, https://doi.org/10.1007/s13277-014-1615-8
  6. Expression of TS, RRM1, ERCC1, TUBB3 and STMN1 Genes in Tissues of Non-small Cell Lung Cancer and its Significance in Guiding Postoperative Adjuvant Chemotherapy vol.16, pp.8, 2015, https://doi.org/10.7314/APJCP.2015.16.8.3189
  7. Evaluation of Machine Learning Algorithm Utilization for Lung Cancer Classification Based on Gene Expression Levels vol.17, pp.2, 2016, https://doi.org/10.7314/APJCP.2016.17.2.835
  8. in NSCLC vol.44, pp.1, 2016, https://doi.org/10.1177/0300060515607383
  9. Clinical significance of UGT1A1 polymorphism and expression of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A in gastric cancer vol.17, pp.1, 2017, https://doi.org/10.1186/s12876-016-0561-x