Proteins involved in DNA damage response pathways and survival of stage 1 non-small-cell lung cancer patients
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- Jeon, Young June
- Publication Year
- 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
Patients and 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
Key words: DNA damage response, non-small-cell lung cancer, prognosis, stage I
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