XPG mRNA Expression Levels Modulate Prognosis in Resected Non-Small-Cell Lung Cancer in Conjunction with BRCA1 and ERCC1 Expression

被引:52
作者
Bartolucci, Roberta [2 ]
Wei, Jia [3 ]
Sanchez, Jose Javier [4 ]
Perez-Roca, Laia
Chaib, Imane
Puma, Francesco [2 ]
Farabi, Raffaele [2 ]
Mendez, Pedro
Roila, Fausto [2 ]
Okamoto, Tatsuro
Taron, Miquel [5 ]
Rosell, Rafael [1 ,5 ]
机构
[1] Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, Med Oncol Serv, Barcelona 08916, Spain
[2] Azienda Osped Santa Maria, Terni, Italy
[3] Nanjing Univ, Sch Med, Drum Tower Hosp, Nanjing, Peoples R China
[4] Autonomous Univ Madrid, Madrid, Spain
[5] Univ Dexeus, Pangaea Biotech, USP Inst, Barcelona, Spain
关键词
DNA repair; Homologous recombination repair; Nucleotide excision repair; Xeroderma pigmentosum group G; DNA-DAMAGE; HUMAN BREAST; REPAIR; SURVIVAL; SIGNATURE; ONCOGENE; PATHWAYS; MELANOMA; TRIAL;
D O I
10.3816/CLC.2009.n.007
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Molecular markers can help identify patients with early-stage non-small-cell lung cancer (NSCLC) with a high risk of relapse. Excision repair cross-complementing 1 (ERCC1), Xeroderma pigmentosum group G (XPG), and breast cancer 1 (BRCA1) are involved in DNA damage repair, whereas ribonucleotide reductase M1 (RRM1) is implicated in DNA synthesis. Expression levels of these molecules might therefore have a prognostic role in lung cancer. Patients and Methods: We examined ERCC1, RRM1, XPG, and BRCA1 mRNA levels by real-time quantitative polymerase chain reaction in 54 patients with stage IB-IIB resected NSCLC. A strong correlation was observed between the 4 genes. Results: For patients with low BRCA1, regardless of XPG mRNA expression levels, disease-free survival (DFS) was not reached. For patients with intermediate/high BRCA1 and high XPG, DFS was 50.7 months. However, for patients with intermediate/high BRCA1 and low/intermediate XPG, DFS decreased to 16.3 months (P = .002). Similar differences were observed in overall survival, with median survival not reached for patients with low BRCA1, regardless of XPG levels, or for patients with intermediate/high BRCA1 and high XPG. Conversely, for patients with intermediate/high BRCA1 levels and low/intermediate XPG levels, median survival dropped to 25.5 months (P = .007). Conclusion: BRCA1 and XPG were identified as independent prognostic factors for both median survival and DFS. High BRCA1 mRNA expression confers poor prognosis in early NSCLC, and the combination of high BRCA1 and low XPG expression still further increases the risk of shorter survival. These findings can help optimize the customization of adjuvant chemotherapy.
引用
收藏
页码:47 / 52
页数:6
相关论文
共 36 条
[1]   TFIIH is negatively regulated by cdk8-containing mediator complexes [J].
Akoulitchev, S ;
Chuikov, S ;
Reinberg, D .
NATURE, 2000, 407 (6800) :102-106
[2]   Hypoxia, DNA repair and genetic instability [J].
Bristow, Robert G. ;
Hill, Richard P. .
NATURE REVIEWS CANCER, 2008, 8 (03) :180-192
[3]  
Britten RA, 2000, INT J CANCER, V89, P453, DOI 10.1002/1097-0215(20000920)89:5<453::AID-IJC9>3.0.CO
[4]  
2-E
[5]   BRCC36 is essential for ionizing radiation-induced BRCA1 phosphorylation and nuclear foci formation [J].
Chen, Xiaowei ;
Arciero, Cletus A. ;
Wang, Chunrong ;
Broccoli, Dominique ;
Godwin, Andrew K. .
CANCER RESEARCH, 2006, 66 (10) :5039-5046
[6]  
Choy H, 2006, ONCOLOGY EVIDENCE BA, P545
[7]   Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression:: A phase III trial in non-small-cell lung cancer [J].
Cobo, Manuel ;
Isla, Dolores ;
Massuti, Bartomeu ;
Montes, Ana ;
Miguel Sanchez, Jose ;
Provencio, Mariano ;
Vinolas, Nuria ;
Paz-Ares, Luis ;
Lopez-Vivanco, Guillermo ;
Angel Munoz, Miguel ;
Felip, Enriqueta ;
Alberola, Vicente ;
Camps, Carlos ;
Domine, Manuel ;
Sanchez, Jose Javier ;
Sanchez-Ronco, Maria ;
Danenberg, Kathleen ;
Taron, Miquel ;
Gandara, David ;
Rosell, Rafael .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (19) :2747-2754
[8]   BCR/ABL and other kinases from chronic myeloproliferative disorders stimulate single-strand annealing, an unfaithful DNA double-strand break repair [J].
Cramer, Kimberly ;
Nieborowska-Skorska, Margaret ;
Koptyra, Mateusz ;
Slupianek, Artur ;
Penserga, Emir Tyrone P. ;
Eaves, Connie J. ;
Aulitzky, Walter ;
Skorski, Tomasz .
CANCER RESEARCH, 2008, 68 (17) :6884-6888
[9]  
DEEB KK, 2007, CANCER RES, V67, P10067
[10]   Identification of an integrated SV40 T/t-antigen cancer signature in aggressive human breast, prostate, and lung carcinomas with poor prognosis [J].
Deeb, Kristin K. ;
Michalowska, Aleksandra M. ;
Yoon, Cheol-yong ;
Krummey, Scott M. ;
Hoenerhoff, Mark J. ;
Kavanaugh, Claudine ;
Li, Ming-chung ;
Demayo, Francesco J. ;
Linnoila, Ilona ;
Deng, Chu-xia ;
Lee, Eva Y. -H. P. ;
Medina, Daniel ;
Shih, Joanna H. ;
Green, Jeffrey E. .
CANCER RESEARCH, 2007, 67 (17) :8065-8080