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细胞角蛋白-1单核苷酸多态性及蛋白水平在声带白斑和喉鳞状细胞癌易感性中的意义

Significance of Cytokeratin-1 Single-Nucleotide Polymorphism and Protein Level in Susceptibility to Vocal Leukoplakia and Laryngeal Squamous Cell Carcinoma.

作者信息

Yang Yue, Zhou Jian, Wu Haitao

机构信息

Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.

Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.

出版信息

ORL J Otorhinolaryngol Relat Spec. 2019;81(2-3):121-129. doi: 10.1159/000497747. Epub 2019 May 8.

Abstract

OBJECTIVE

To investigate the association between the cytokeratin (CK)-1 single-nucleotide polymorphism (SNP), the protein level of CK-1 and the risk of vocal leukoplakia and laryngeal squamous cell carcinoma (LSCC).

METHODS

In this case-control study, 155 patients with vocal leukoplakia, 323 patients with LSCC, and 266 healthy controls were genotyped for the CK-1 (SNP RS14024) gene using pyrosequencing. The protein expression level of CK-1 was analyzed in vocal leukoplakia, LSCC, and vocal polyp patients by immunohistochemistry (IHC).

RESULTS

Of the CK-1 RS14024 polymorphism, the heterozygote AG and homozygote GG genotype exhibited a significantly increased risk of LSCC (AG: OR = 2.16, p = 0.014; GG: OR = 2.15, p = 0.018) compared to normal controls. A higher protein expression level of CK-1 was detected in patients with LSCC compared to vocal leukoplakia and polyps (both p < 0.001), and a significant increasing trend of CK-1 protein expression level from mild-moderate dysplasia to moderate-severe dysplasia in vocal leukoplakia patients was also observed (p = 0.006).

CONCLUSIONS

This study demonstrates that the CK-1 SNP and high protein expression levels are associated with vocal leukoplakia and LSCC and promote the transformation from vocal leukoplakia to LSCC in a Chinese Han population.

摘要

目的

探讨细胞角蛋白(CK)-1单核苷酸多态性(SNP)、CK-1蛋白水平与声带白斑及喉鳞状细胞癌(LSCC)风险之间的关联。

方法

在这项病例对照研究中,采用焦磷酸测序法对155例声带白斑患者、323例LSCC患者及266例健康对照者的CK-1(SNP RS14024)基因进行基因分型。通过免疫组织化学(IHC)分析声带白斑、LSCC及声带息肉患者中CK-1的蛋白表达水平。

结果

对于CK-1 RS14024多态性,与正常对照相比,杂合子AG和纯合子GG基因型的LSCC风险显著增加(AG:比值比[OR]=2.16,p=0.014;GG:OR=2.15,p=0.018)。与声带白斑和息肉患者相比,LSCC患者中检测到更高的CK-1蛋白表达水平(均p<0.001),并且在声带白斑患者中也观察到从轻度-中度发育异常到中度-重度发育异常的CK-1蛋白表达水平有显著上升趋势(p=0.006)。

结论

本研究表明,CK-1 SNP和高蛋白表达水平与声带白斑和LSCC相关,并促进中国汉族人群中声带白斑向LSCC的转变。

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