MTH1表达与接受手术切除的肺癌患者肿瘤恶性潜能及预后不良的相关性

Association of MTH1 expression with the tumor malignant potential and poor prognosis in patients with resected lung cancer.

作者信息

Fujishita Takatoshi, Okamoto Tatsuro, Akamine Takaki, Takamori Shinkichi, Takada Kazuki, Katsura Masakazu, Toyokawa Goji, Shoji Fumihiro, Shimokawa Mototsugu, Oda Yoshinao, Nakabeppu Yusaku, Maehara Yoshihiko

机构信息

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Lung Cancer. 2017 Jul;109:52-57. doi: 10.1016/j.lungcan.2017.04.012. Epub 2017 Apr 24.

DOI:10.1016/j.lungcan.2017.04.012

PMID:28577950

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.

摘要

目的

氧化嘌呤核苷三磷酸酶，MutT同源物1（MTH1）在生理上可清除核苷酸池中的8-氧代-dGTP。先前的研究表明，MTH1与非小细胞肺癌（NSCLC）细胞系中的肿瘤增殖和侵袭有关；然而，MTH1在NSCLC患者中的作用仍不清楚。

材料与方法

回顾性研究了在我院接受NSCLC手术的两个患者队列。在一个由197例患者组成的队列中，分析了MTH1表达与临床病理因素或预后之间的关联。在另一个由41例患者组成的队列中，分析了肿瘤中MTH1表达与患者血清氧化应激水平（通过戴克隆活性氧代谢产物[d-ROMs]试验评估）或抗氧化能力（通过生物抗氧化潜力[BAP]试验评估）之间的关系。使用免疫组织化学对总共238例患者的MTH1蛋白水平进行了评估。

结果

在前一个队列的197例患者中，111例（56.3%）表现出高MTH1表达，而86例（43.7%）表现出低MTH1表达。男性、吸烟史≥20包年、鳞状细胞癌、病理分期≥II期、肿瘤直径≥30mm、淋巴结转移、胸膜侵犯、淋巴管浸润和血管浸润与高MTH1表达显著相关（p < 0.05）。高MTH1表达组的预后明显比低MTH1表达组差（5年总生存率：81.6%对92.3%，p = 0.0011；5年无病生存率：55.0%对83.7%，p = 0.0002）。高MTH1表达组的d-ROMs和BAP试验值显著高于低MTH1表达组（p < 0.05）。