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: ジャーナルへの寄稿記事

10 引用 (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.

元の言語英語
ページ(範囲)258-266
ページ数9
ジャーナルCancer Medicine
6
発行部数1
DOI
出版物ステータス出版済み - 1 1 2017

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Neoplasms
Survival
Pyrophosphatases
Messenger RNA
Neoadjuvant Therapy
Mitochondrial DNA
Alcohol Drinking
Paraffin
Reverse Transcription
Oxidative Stress
Epithelium
Nucleotides
Smoking
Esophageal Squamous Cell Carcinoma
Polymerase Chain Reaction
8-oxo-7-hydrodeoxyguanosine
Therapeutics
Proteins
deoxyguanosine triphosphate
triphosphoric acid

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

これを引用

Prognostic impact of MutT homolog-1 expression on esophageal squamous cell carcinoma. / Akiyama, Shingo; Saeki, Hiroshi; Nakashima, Yuichiro; Iimori, Makoto; Kitao, Hiroyuki; Oki, Eiji; Oda, Yoshinao; Nakabeppu, Yusaku; Kakeji, Yoshihiro; Maehara, Yoshihiko.

:: Cancer Medicine, 巻 6, 番号 1, 01.01.2017, p. 258-266.

研究成果: ジャーナルへの寄稿記事

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abstract = "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.",
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AU - Saeki, Hiroshi

AU - Nakashima, Yuichiro

AU - Iimori, Makoto

AU - Kitao, Hiroyuki

AU - Oki, Eiji

AU - Oda, Yoshinao

AU - Nakabeppu, Yusaku

AU - Kakeji, Yoshihiro

AU - Maehara, Yoshihiko

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