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T. Tagawa
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-091 - Biological Significance of CHK2 Gene Expression in Lung Adenocarcinoma (ID 2469)
09:30 - 17:00 | Author(s): T. Tagawa
- Abstract
Background:
CHK2 is a transducer protein that is involved in DNA damage response (DDR). CHK2 phosphorylates effector proteins that play roles in DNA repair, cell cycle regulation and apoptosis. Recently, CHK2 have been found to have a critical role in the mitosis, and disruption of CHK2-BRCA pathway caused chromosomal instability in colon cancer cell lines (Stolz et al. Nat Cell Biol 2010:12; 492). The purpose of this study was to investigate the biological role of CHK2 and related factors in lung adenocarcinoma.
Methods:
We investigated 60 surgically resected lung adenocarcinomas. CHK2 and BRCA1 mRNA expression levels were evaluated by qRT-PCR. Relative mRNA expression levels of each sample were standardized to those of β-actin. EGFR mutation (exon 19 deletion and 21 point mutation) was detected by PNA-LNA PCR clamp method. KRAS mutation (exon 2, codon 12, 13) and p53 mutation (exon 5-9) were examined by direct sequencing. p27 and p21 protein expression levels were assessed by immunohistochemistry. Chromosomal aberration (CA) was examined in 20 samples with single-nucleotide polymorphism–CGH (SNP–CGH).
Results:
CHK2 mRNA levels were significantly increased in the tumor tissues compared to the normal tissues (p=0.012). CHK2 mRNA level was not correlated with patients’ clinicopathological factors, EGFR mutation status or p53 mutation status. CHK2 mRNA levels were significantly correlated with BRCA1 mRNA levels (ρ = 0.569, p < 0.0001). High CHK2 mRNA expression and high p27 protein expression levels were associated with poor prognosis for recurrence free survival (P = 0.028, P = 0.048), although both expression levels were not correlated with each other. 7 samples were determined to be high CA, while 13 samples to be low CA according to SNP-CGH. CHK2 mRNA level was higher in high CA (7 samples) than in low CA samples (13 samples) (Ave. 0.326 vs. 0.185; p=0.0129).
Conclusion:
CHK2 mRNA expression level was increased in lung adenocarcinoma and was related to poor prognostic outcomes. CHK2 pathway may be important for the proliferation of lung adenocarcinoma, especially in tumors with chromosomal instability.
