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

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.

SUBMITTER: Akiyama S

PROVIDER: S-EPMC5269568 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Akiyama Shingo S Saeki Hiroshi H Nakashima Yuichiro Y Iimori Makoto M Kitao Hiroyuki H Oki Eiji E Oda Yoshinao Y Nakabeppu Yusaku Y Kakeji Yoshihiro Y Maehara Yoshihiko Y

Cancer medicine 20161205 1

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 es ...[more]

PMID: 27917618

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Project description:BackgroundAbsent in melanoma 1-like (AIM1L), also known as crystalline beta gamma domain containing 2. The relationship between AIM1L and tumors has not been fully investigated, and the biological function of AIM1L in different tumors is unknown, so we bioinformatically explored a possible relationship between AIM1L and esophageal squamous cell carcinoma (ESCC).MethodsAIM1L mRNA expression was detected by the Gene Expression Omnibus database (GSE20347, GSE161533, and GSE53625), and protein level expression was detected by immunohistochemistry. The correlation between AIM1L expression and clinical pathological characteristics was evaluated by the Wilcoxon signed rank test or chi-square test. Kaplan-Meier analysis and Cox proportional risk regression model were used to determine the prognostic value of AIM1L in ESCC patients and establish and verify a nomogram. Find genes highly related to the expression of AIM1L, conduct GO and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and conduct GSEA analysis on the gene set. The "CIBERSORT" R package was used to explore the relationship between AIM1L and immune infiltration, and the "OncoPredict" R package was used to explore the relationship between AIM1L and drug sensitivity.ResultsCompared with the matched adjacent non-cancer tissues, the expression of AIM1L was down-regulated in ESCC tissues, and correlated with tumor grade. Kaplan-Meier survival analysis and Cox analysis showed that the low expression of AIM1L was related to the poor prognosis of ESCC patients. Enrichment analysis explained the possible function of AIM1L, GSEA determined the highly correlated signal pathway of AIM1L low expression phenotype, immune infiltration analysis determined that AIM1L was related to activated NK cells and macrophage M2, and drug sensitivity analysis determined that the low expression of AIM1L might be related to EGFR targeted drug resistance.ConclusionAIM1L may be a candidate tumor suppressor gene for ESCC and an independent molecular biomarker for the prognosis of ESCC patients.

Dataset Information

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

Publications

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

Similar Datasets

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