Prognostic impact of MutT homolog-1 expression on esophageal squamous cell carcinoma

Shingo Akiyama, Hiroshi Saeki, Yuichiro Nakashima, Makoto Iimori, Hiroyuki Kitao, Eiji Oki, Yoshinao Oda, Yusaku Nakabeppu, Yoshihiro Kakeji, Yoshihiko Maehara

研究成果: Contribution to journalArticle査読

22 被引用数 (Scopus)

抄録

MutT homolog-1 (MTH1) is a pyrophosphatase that acts on oxidized nucleotides and hydrolyzes 8-oxo-2’-deoxyguanosine triphosphate in deoxynucleoside triphosphate pool to prevent its incorporation into nuclear and mitochondrial DNA, result in reduce cytotoxicity in tumor cells. MTH1 is overexpressed in various cancers and is considered as a therapeutic target. Environmental factors such as cigarette smoking and alcohol consumption are critical risk factors for the development and progression of esophageal squamous cell carcinoma (ESCC), suggesting that oxidative stress contributes to the pathogenesis of ESCC. We examined the expression of MTH1 and the accumulation of 8-oxo-2’-deoxyguanosine (8-oxo-dG) in 84 patients with ESCC who underwent curative resection without neoadjuvant therapy. MTH1 mRNA level was quantified by performing quantitative reverse transcription-PCR. Immunohistochemical analysis of paraffin-embedded cancer tissues was performed to determine MTH1 protein expression and 8-oxo-dG accumulation. MTH1 mRNA expression was higher in cancerous tissues than in the corresponding normal epithelium (P < 0.0001). Immunohistochemical analysis showed that high MTH1 expression was significantly associated with deeper tumor invasion and venous invasion, advanced cancer stage, and poor overall survival (P = 0.0021) and disease-specific survival (P = 0.0013) compared with low MTH1 expression. Furthermore, high MTH1 expression was an independent predictor of poor disease-specific survival (P = 0.0121). In contrast, 8-oxo-dG accumulation was not associated with any clinicopathological factor and poor prognosis. These results suggest that MTH1 overexpression is a predictor of ESCC progression and poor prognosis and that MTH1 can serve as a therapeutic target for treating patients with ESCC.

本文言語英語
ページ(範囲)258-266
ページ数9
ジャーナルCancer Medicine
6
1
DOI
出版ステータス出版済み - 1 1 2017

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 放射線学、核医学およびイメージング
  • 癌研究

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