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口腔鳞状细胞癌中组织和唾液烟酰胺 N-甲基转移酶的分析:为开发用于早期疾病的非侵入性诊断试验奠定基础。

Analysis of tissue and salivary nicotinamide N-methyltransferase in oral squamous cell carcinoma: basis for the development of a noninvasive diagnostic test for early-stage disease.

机构信息

Department of Clinical Sciences, Polytechnic University of Marche, I-60131 Ancona, Italy.

出版信息

Biol Chem. 2012 May;393(6):505-11. doi: 10.1515/hsz-2012-0112.

Abstract

Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancer worldwide. In recent decades, the 5-year mortality rate is approximately 50% around the world. As reliable biomarkers of oral cancer are still lacking, it is necessary to identify new target molecules for early diagnosis, effective therapy, and monitoring of the disease. In the present work, we focused on the expression of the enzyme nicotinamide N-methyltransferase (NNMT). We analyzed enzyme activity in 37 paired tumor and non-tumor tissues and found that activity levels are significantly higher in tumor compared with adjacent normal oral mucosa. Interestingly, oral epithelium surrounding tumor of unfavorable cases (N+) seems to display higher activity levels compared with that of favorable ones (N0). Western blot analyses were performed to evaluate protein levels in saliva samples from patients with OSCC and healthy subjects. Preliminary results indicated an up-regulation of salivary NNMT in tumor. This study shows a marked increase in enzyme activity in oral cancer and suggests that adjacent normal tissue of unfavorable cases seems to change toward cancer. Moreover, it is conceivable to hypothesize that NNMT could represent a potential biomarker for early and non-invasive diagnosis of oral cancer.

摘要

口腔鳞状细胞癌(OSCC)是全球最常见的头颈部癌症。近几十年来,全球范围内的 5 年死亡率约为 50%。由于可靠的口腔癌生物标志物仍然缺乏,因此有必要鉴定新的靶分子以用于早期诊断、有效治疗和疾病监测。在本工作中,我们重点研究了酶烟酰胺 N-甲基转移酶(NNMT)的表达。我们分析了 37 对肿瘤和非肿瘤组织中的酶活性,发现与相邻正常口腔黏膜相比,肿瘤中的活性水平明显更高。有趣的是,与有利病例(N0)相比,不良病例(N+)肿瘤周围的口腔上皮似乎显示出更高的活性水平。进行了 Western blot 分析以评估来自 OSCC 患者和健康受试者的唾液样本中的蛋白水平。初步结果表明肿瘤中唾液 NNMT 的上调。这项研究表明口腔癌中酶活性显著增加,并表明不良病例的相邻正常组织似乎向癌症转变。此外,可以设想 NNMT 可能代表用于早期和非侵入性诊断口腔癌的潜在生物标志物。

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