Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients

被引：25

作者：

Choi, C. M. ^{[2
]}

Yang, S. C. ^{[3
]}

Jo, H. J. ^{[4
]}

Song, S. Y. ^{[5
]}

Jeon, Y. J. ^{[6
]}

Jang, T. W. ^{[7
]}

Kim, D. J. ^{[8
]}

Jang, S. H. ^{[9
]}

Yang, S. H. ^{[10
]}

Kim, Y. D. ^{[11
]}

Lee, K. H. ^{[12
]}

Jang, S. J. ^{[13
]}

Kim, Y. T. ^{[14
]}

Kim, D. K. ^{[15
]}

Chung, D. H. ^{[16
]}

Kim, L. ^{[17
]}

Nam, H. S.

Cho, J. H.

Kim, H. J.

Ryu, J. S. ^{[1
]}

机构：

[1] Inha Univ, Dept Internal Med, Sch Med, Ctr Lung Canc,Inha Univ Hosp,Pulm Div, Jung Gu 400103, Incheon, South Korea

[2] Univ Ulsan, Coll Med, Dept Pulm & Crit Care Med, Asan Med Ctr, Seoul, South Korea

[3] Seoul Natl Univ, Coll Med, Dept Internal Med, Div Pulm & Crit Care Med, Seoul 151, South Korea

[4] Wonkwang Univ, Dept Pathol, Coll Med, Iksan, South Korea

[5] Chonnam Natl Univ, Hwasun Hosp, Dept Thorac & Cardiovasc Surg, Hwasun Gun, South Korea

[6] Keimyung Univ, Sch Med, Dept Internal Med, Taegu, South Korea

[7] Kosin Univ, Coll Med, Dept Internal Med, Pusan, South Korea

[8] Soonchunhyang Univ Hosp, Div Resp & Allergy Med, Coll Med, Puchon, South Korea

[9] Hallym Univ, Coll Med, Div Pulm Allergy & Crit Care Med, Sacred Heart Hosp, Anyang, South Korea

[10] Wonkwang Univ Hosp, Dept Internal Med, Iksan, South Korea

[11] Pusan Natl Univ, Sch Med, Dept Thorac Surg, Pusan, South Korea

[12] Yeungnam Univ, Sch Med, Dept Internal Med, Taegu, South Korea

[13] Univ Ulsan, Coll Med, Dept Pathol, Asan Med Ctr, Seoul, South Korea

[14] Seoul Natl Univ, Coll Med, Dept Thorac & Cardiovasc Surg, Seoul, South Korea

[15] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Thorac & Cardiovasc Surg, Seoul, South Korea

[16] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul, South Korea

[17] Inha Univ Hosp, Dept Pathol, Inchon, South Korea

来源：

ANNALS OF ONCOLOGY | 2012年 / 23卷 / 08期

关键词：

DNA damage response; non-small-cell lung cancer; prognosis; stage I; REPAIR; ERCC1; ACTIVATION; MUTATIONS;

D O I：

10.1093/annonc/mdr606

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Biological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue. Expression of several proteins (ATM, ATMpS1981, gamma H2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients. Low expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of gamma H2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for gamma H2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients. The proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.

引用

页码：2088 / 2093

页数：6

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