Rodrigues P R S, Maia L L, Santos M, Peterle G T, Alves L U, Takamori J T, Souza R P, Barbosa W M, Mercante A M C, Nunes F D, Carvalho M B, Tajara E H, Louro I D, Silva-Conforti A M A
Laboratório de Biologia Molecular, Hospital Heliópolis, São Paulo, SP, Brasil.
Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
Genet Mol Res. 2015 Nov 25;14(4):14979-88. doi: 10.4238/2015.November.24.5.
The leptin gene product is released into the blood stream, passes through the blood-brain barrier, and finds the leptin receptor (LEPR) in the central nervous system. This hormone regulates food intake, hematopoiesis, inflammation, immunity, differentiation, and cell proliferation. The LEPR Gln223Arg polymorphism has been reported to alter receptor function and expression, both of which have been related with prognostics in several tumor types. Furthermore, several studies have shown a relationship between the Gln223Arg polymorphism and tumor development, and its role in oral and oropharyngeal squamous cell carcinoma is now well understood. In this study, 315 DNA samples were used for LEPR Gln223Arg genotyping and 87 primary oral and oropharyngeal squamous cell carcinomas were used for immunohistochemical expression analysis, such that a relationship between these and tumor development and prognosis could be established. Homozygous LEPR Arg223 was found to be associated with a 2-fold reduction in oral and oropharyngeal cancer risk. In contrast, the presence of the Arg223 allele in tumors was associated with worse disease-free and disease-specific survival. Low LEPR expression was found to be an independent risk factor, increasing the risk for lymph node metastasis 4-fold. In conclusion, the Gln223Arg polymorphism and LEPR expression might be valuable markers for oral and oropharyngeal cancer, suggesting that LEPR might serve as a potential target for future therapies.
瘦素基因产物释放到血流中，穿过血脑屏障，并在中枢神经系统中找到瘦素受体（LEPR）。这种激素调节食物摄入、造血、炎症、免疫、分化和细胞增殖。据报道，LEPR Gln223Arg多态性会改变受体功能和表达，这两者都与几种肿瘤类型的预后有关。此外，多项研究表明Gln223Arg多态性与肿瘤发展之间存在关联，其在口腔和口咽鳞状细胞癌中的作用现已得到充分了解。在本研究中，315份DNA样本用于LEPR Gln223Arg基因分型，87例原发性口腔和口咽鳞状细胞癌用于免疫组化表达分析，从而确定它们与肿瘤发展和预后之间的关系。发现纯合子LEPR Arg223与口腔和口咽癌风险降低2倍有关。相反，肿瘤中Arg223等位基因的存在与无病生存期和疾病特异性生存期较差有关。发现低LEPR表达是一个独立的危险因素，使淋巴结转移风险增加4倍。总之，Gln223Arg多态性和LEPR表达可能是口腔和口咽癌的有价值标志物，表明LEPR可能成为未来治疗的潜在靶点。
