Takatoshi Fujishita1, Tatsuro Okamoto2, Takaki Akamine1, Shinkichi Takamori1, Kazuki Takada3, Masakazu Katsura1, Goji Toyokawa1, Fumihiro Shoji1, Mototsugu Shimokawa4, Yoshinao Oda5, Yusaku Nakabeppu6, Yoshihiko Maehara1. 1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: tatsuro@surg2.med.kyushu-u.ac.jp. 3. 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. 4. Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan. 5. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 6. Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Abstract
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.
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.
Authors: Govindi J Samaranayake; Clara I Troccoli; Ling Zhang; Mai Huynh; Christina J Jayaraj; Debin Ji; Lisa McPherson; Yoshiyuki Onishi; Dao M Nguyen; David J Robbins; Mahsa Karbaschi; Marcus S Cooke; Antonio Barrientos; Eric T Kool; Priyamvada Rai Journal: Mol Cancer Ther Date: 2019-11-19 Impact factor: 6.261
Authors: Huaping Chen; Sadia Afrin; Yingqiu Guo; Wenhua Chu; Tammie L S Benzinger; Buck E Rogers; Joel R Garbow; Joel S Perlmutter; Dong Zhou; Jinbin Xu Journal: Int J Mol Sci Date: 2020-11-23 Impact factor: 5.923