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


METHODS
Expression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients.


RESULTS
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 γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 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.


CONCLUSIONS
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.
Department of Pulmonary and Critical Care Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul.
C M
CM
Choi
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul.
S C
SC
Yang
Department of Pathology, College of Medicine, Wonkwang University, Iksan.
H J
HJ
Jo
Department of Thoracic and Cardiovascular Surgery, Chonnam National University Hwasun Hospital, Hwasun-gun.
S Y
SY
Song
Department of Internal Medicine, School of Medicine, Keimyung University, Daegu.
Y J
YJ
Jeon
Department of Internal Medicine, College of Medicine, Kosin University, Busan.
T W
TW
Jang
Division of Respiratory and Allergy Medicine, Soonchunhyang University Hospital, College of Medicine, Bucheon.
D J
DJ
Kim
Division of Pulmonary, Allergy & Critical Care Medicine, Hallym University Sacred Heart Hospital, College of Medicine, Hallym University, Anyang.
S H
SH
Jang
Department of Internal Medicine, Wonkwang University Hospital, Iksan.
S H
SH
Yang
Department of Thoracic Surgery, School of Medicine, Pusan National University, Busan.
Y D
YD
Kim
Department of Internal Medicine, Yeungnam University School of Medicine, Daegu.
K H
KH
Lee
Department of Pathology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul.
S J
SJ
Jang
Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul.
Y T
YT
Kim
Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul.
D K
DK
Kim
Department of Pathology, Seoul National University College of Medicine, Seoul.
D H
DH
Chung
Department of Pathology.
L
L
Kim
Pulmonary Division, Department of Internal Medicine, Inha University Hospital, Incheon, Korea.
H S
HS
Nam
Pulmonary Division, Department of Internal Medicine, Inha University Hospital, Incheon, Korea.
J H
JH
Cho
Pulmonary Division, Department of Internal Medicine, Inha University Hospital, Incheon, Korea.
H J
HJ
Kim
Pulmonary Division, Department of Internal Medicine, Inha University Hospital, Incheon, Korea. Electronic address: jsryu@inha.ac.kr.
J S
JS
Ryu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004249:DNA Damage; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D015996:Survival Rate
D009363:Neoplasm Proteins