PMID- 28577950 OWN - NLM STAT- MEDLINE DCOM- 20180309 LR - 20220410 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 109 DP - 2017 Jul TI - Association of MTH1 expression with the tumor malignant potential and poor prognosis in patients with resected lung cancer. PG - 52-57 LID - S0169-5002(17)30299-4 [pii] LID - 10.1016/j.lungcan.2017.04.012 [doi] AB - OBJECTIVES: The oxidized purine nucleoside triphosphatase, mutT homolog 1 (MTH1), physiologically sanitizes 8-oxo-dGTP in the nucleotide pool. Previous studies indicated that MTH1 is associated with tumor proliferation and invasion in non-small cell lung cancer (NSCLC) cell lines; however, the role of MTH1 in patients with NSCLC remains unclear. MATERIALS AND METHODS: Two patient cohorts that underwent surgery for NSCLC in our institution were investigated retrospectively. In one cohort consisting of 197 patients, the associations between MTH1 expression and clinicopathological factors or prognosis were analyzed. In another cohort consisting of 41 patients, the relationship between MTH1 expression in the tumors and serum oxidative stress levels (evaluated by the diacron-reactive oxygen metabolites [d-ROMs] test) or antioxidant capacity in the patients (evaluated by the biological antioxidant potential (BAP) test) was analyzed. A total of 238 patients were assessed for MTH1 protein levels using immunohistochemistry. RESULTS: Among the 197 patients in the former cohort, 111 (56.3%) exhibited high MTH1 expression, while 86 (43.7%) exhibited low MTH1 expression. Male sex, smoking habit of >/=20 pack-years, squamous cell carcinoma, pathological stage >/= II, tumor diameter >/=30mm, lymph node metastases, pleural invasion, lymphatic permeation and vascular infiltration were significantly associated with high MTH1 expression (p<0.05). The high MTH1 expression group had a significantly worse prognosis than that of the low MTH1 expression group (5-year overall survival: 81.6% vs. 92.3%, p=0.0011; 5-year disease-free survival: 55.0% vs. 83.7%, p=0.0002). d-ROMs and BAP test values were significantly higher in the high than in the low MTH1 expression group (p<0.05). CONCLUSION: This study showed that MTH1 protein expression was closely related to factors associated with a high malignant potential and poor patient survival. MTH1 may be a novel therapeutic target for NSCLC. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Fujishita, Takatoshi AU - Fujishita T AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Okamoto, Tatsuro AU - Okamoto T AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: tatsuro@surg2.med.kyushu-u.ac.jp. FAU - Akamine, Takaki AU - Akamine T AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Takamori, Shinkichi AU - Takamori S AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Takada, Kazuki AU - Takada K AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Katsura, Masakazu AU - Katsura M AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Toyokawa, Goji AU - Toyokawa G AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Shoji, Fumihiro AU - Shoji F AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Shimokawa, Mototsugu AU - Shimokawa M AD - Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan. FAU - Oda, Yoshinao AU - Oda Y AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Nakabeppu, Yusaku AU - Nakabeppu Y AD - Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. FAU - Maehara, Yoshihiko AU - Maehara Y AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. LA - eng PT - Journal Article DEP - 20170424 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Deoxyguanine Nucleotides) RN - 139307-94-1 (8-oxodeoxyguanosine triphosphate) RN - EC 3.1.3.2 (Phosphoric Monoester Hydrolases) RN - EC 3.6.1.55 (8-oxodGTPase) RN - EC 6.5.1.- (DNA Repair Enzymes) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinogenesis MH - Carcinoma, Non-Small-Cell Lung/*diagnosis/genetics/mortality MH - Cohort Studies MH - DNA Repair Enzymes/genetics/*metabolism MH - Deoxyguanine Nucleotides/metabolism MH - Female MH - Follow-Up Studies MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Lung Neoplasms/*diagnosis/genetics/mortality MH - Male MH - Middle Aged MH - Oxidative Stress MH - Phosphoric Monoester Hydrolases/genetics/*metabolism MH - Pneumonectomy MH - Prognosis MH - Survival Analysis MH - Up-Regulation OTO - NOTNLM OT - MutT Homolog 1 (MTH1) OT - Non-small cell lung cancer (NSCLC) OT - Oxidative stress OT - Surgery EDAT- 2017/06/05 06:00 MHDA- 2018/03/10 06:00 CRDT- 2017/06/05 06:00 PHST- 2016/11/19 00:00 [received] PHST- 2017/03/13 00:00 [revised] PHST- 2017/04/18 00:00 [accepted] PHST- 2017/06/05 06:00 [entrez] PHST- 2017/06/05 06:00 [pubmed] PHST- 2018/03/10 06:00 [medline] AID - S0169-5002(17)30299-4 [pii] AID - 10.1016/j.lungcan.2017.04.012 [doi] PST - ppublish SO - Lung Cancer. 2017 Jul;109:52-57. doi: 10.1016/j.lungcan.2017.04.012. Epub 2017 Apr 24.