Open AccessPrognostic impact of MutT homolog‐1 expression on esophageal squamous cell carcinoma
Author(s) -
Akiyama Shingo,
Saeki Hiroshi,
Nakashima Yuichiro,
Iimori Makoto,
Kitao Hiroyuki,
Oki Eiji,
Oda Yoshinao,
Nakabeppu Yusaku,
Kakeji Yoshihiro,
Maehara Yoshihiko
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.979
Subject(s) - cancer research , immunohistochemistry , transcription factor , biology , cancer , deoxyguanosine , oxidative stress , gene , immunology , endocrinology , biochemistry , genetics
MutT homolog‐1 ( MTH 1) 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. MTH 1 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 MTH 1 and the accumulation of 8‐oxo‐2’‐deoxyguanosine (8‐oxo‐ dG ) in 84 patients with ESCC who underwent curative resection without neoadjuvant therapy. MTH 1 mRNA level was quantified by performing quantitative reverse transcription‐ PCR . Immunohistochemical analysis of paraffin‐embedded cancer tissues was performed to determine MTH 1 protein expression and 8‐oxo‐ dG accumulation. MTH 1 mRNA expression was higher in cancerous tissues than in the corresponding normal epithelium ( P < 0.0001). Immunohistochemical analysis showed that high MTH 1 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 MTH 1 expression. Furthermore, high MTH 1 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 MTH 1 overexpression is a predictor of ESCC progression and poor prognosis and that MTH 1 can serve as a therapeutic target for treating patients with ESCC.