Chen Hung-Chih, Yang Cheng-Mei, Cheng Jiin-Tsuey, Tsai Kuo-Wang, Fu Ting-Ying, Liou Huei-Han, Tseng Hui-Hwa, Lee Jang-Hwa, Li Guan-Cheng, Wang Jyh-Seng, Hou Yu-Yi, Weng Ta-Jung, Ger Luo-Ping
Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan.
J Oral Pathol Med. 2016 Jul;45(6):409-17. doi: 10.1111/jop.12381. Epub 2015 Nov 2.
Oral cancer is the 4th leading cause of cancer death for males and the top cancer in young adult males in Taiwan. Tongue squamous cell carcinoma (TSCC) is a common oral cancer and generally associated with poor prognosis. Global DNA hypomethylation at the 5 position of cytosine (5mC) is a well-known epigenetic feature of cancer. Therefore, the purpose of this study was to investigate the relationship of the global 5mC content with the tumorigenesis and prognosis of patients with TSCC.
The levels of global 5mC were evaluated by immunohistochemistry using tissue microarray slides of 248 surgically resected TSCC and 202 corresponding tumor adjacent normal (TAN) tissues.
We found that the level of 5mC in TSCC (P < 0.001) was significantly decreased as compared to TAN. Among TSCC tissues, decreased levels of 5mC were associated with female gender (P = 0.036). In addition, the global hypomethylation was associated with the poor disease-specific survival in TSCC patients (adjusted hazard ratio: 1.55, P = 0.043), especially for patients in older age group (> 50 years, P = 0.013), with moderate or poor cell differentiation (P = 0.044), early stage of disease (I-II, P = 0.046), small tumor size (T1-T2, P = 0.005), without lymph node involvement (P = 0.041), and ever received postoperative radiotherapy (P = 0.009).
Global hypomethylation was an independent biomarker for the development and poor prognosis of TSCC.
口腔癌是台湾男性癌症死亡的第四大主要原因，也是年轻成年男性中最常见的癌症。舌鳞状细胞癌（TSCC）是一种常见的口腔癌，通常预后较差。胞嘧啶第5位的全局DNA低甲基化（5mC）是癌症众所周知的表观遗传特征。因此，本研究的目的是探讨全局5mC含量与TSCC患者肿瘤发生及预后的关系。
使用248例手术切除的TSCC组织微阵列玻片和202例相应的肿瘤邻近正常（TAN）组织，通过免疫组织化学评估全局5mC水平。
我们发现，与TAN相比，TSCC中5mC水平（P < 0.001）显著降低。在TSCC组织中，5mC水平降低与女性性别相关（P = 0.036）。此外，全局低甲基化与TSCC患者较差的疾病特异性生存率相关（调整后的风险比：1.55，P = 0.043），特别是对于年龄较大（> 50岁，P = 有关013）、细胞分化中等或较差（P = 0.044）、疾病早期（I-II期，P = 0.046）、肿瘤较小（T1-T2期，P = 0.005）、无淋巴结转移（P = 0.041）以及曾接受术后放疗的患者（P = 0.009）。
全局低甲基化是TSCC发生发展及预后不良的独立生物标志物。
