Clinical significance of DNA damage response factors and chromosomal instability in primary lung adenocarcinoma

Tatsuro Okamoto, Mikihiro Kohno, Kensaku Ito, Kazuki Takada, Masakazu Katsura, Yosuke Morodomi, Gouji Toyokawa, Fumihiro Shoji, Yoshihiko Maehara

研究成果: Contribution to journalArticle査読

3 被引用数 (Scopus)

抄録

Aim: The purpose of this study was to investigate the biological role of DNA damage-response genes and chromosomal instability in primary lung adenocarcinoma. Materials and Methods: We investigated 60 surgically-resected lung adenocarcinomas. Levels of checkpoint kinase 2 gene (CHEK2) and breast cancer type 1 susceptibility protein gene (BRCA1) mRNA expression were evaluated by polymerase chain reaction (PCR). Epidermal growth factor receptor (EGFR) mutations (exon 19 deletion and exon 21 mutation) were detected by the PCR clamp method. Mutations in Kirsten rat sarcoma viral oncogene homolog gene (KRAS) and TP53 were examined by direct sequencing. Expression levels of p27 and p16 proteins were assessed by immunohistochemistry. Chromosomal aberrations (CA) were examined in 20 samples with single-nucleotide polymorphism-comparative genomic hybridization. Results: CHEK2 mRNA levels were significantly increased in tumor tissues compared to normal tissues (p=0.0123, paired t-test), whereas BRCA mRNA levels were not increased. TP53 mutation positivity and BRCA1 mRNA expression were positively associated with CHEK2 mRNA expression status (p=0.022 and p=0.0008). High CHEK2 mRNA expression was associated with poor recurrence-free survival (p=0.028). CHEK2 mRNA levels were higher in samples with a high CA frequency than in those with a low CA frequency (averages: 0.326 vs. 0.185; p=0.0129). Conclusion: The CHEK2 mRNA expression level was found elevated in lung adenocarcinoma and was related to a poor prognostic outcome. The CHEK2 pathway may be important for the proliferation of lung adenocarcinoma, especially in tumors with chromosomal instability.

本文言語英語
ページ(範囲)1729-1735
ページ数7
ジャーナルAnticancer research
37
4
DOI
出版ステータス出版済み - 4 2017

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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