The incidence of esophageal adenocarcinoma (EAC) has risen rapidly during the past four decades, making it the most common type of esophageal cancer in the USA and Western countries. The NEK (Never in mitosis A (NIMA) related kinase) gene family is a group of serine/threonine kinases with 11 members. Aberrant expression of NEKs has been recently found in a variety of human cancers and plays important roles in tumorigenesis, progression, and drug-resistance. However, the expression of the NEKs in EAC and its precancerous condition (Barrett’s esophagus, BE) has not been investigated. In the present study, we first analyzed the TCGA and 9 GEO databases (a total of 10 databases in which 8 contain EAC and 6 contain BE) using bioinformatic approaches for NEKs expression in EAC and BE. We identified that several NEK members, such as NEK2 (7/8), NEK3 (6/8), and NEK6 (6/8), were significantly upregulated in EAC as compared to normal esophagus samples. Alternatively, NEK1 was downregulated in EAC as compared to the normal esophagus. On the contrary, genomic alterations of these NEKs are not frequent in EAC. We validated the above findings using qRT-PCR and the protein expression of NEKs in EAC cell lines using Western blotting and in primary EAC tissues using immunohistochemistry and immunofluorescence. Our data suggest that frequent upregulation of NEK2, NEK3, and NEK7 may be important in EAC.
食管腺癌（EAC）的发病率在过去四十年间急剧上升，已成为美国和西方国家最常见的食管癌类型。NEK（Never in mitosis A相关激酶）基因家族是一组包含11个成员的丝氨酸/苏氨酸激酶。近期研究发现NEK在多种人类癌症中存在异常表达，并在肿瘤发生、进展及耐药性中发挥重要作用。然而，NEK在EAC及其癌前病变（巴雷特食管，BE）中的表达尚未得到研究。本研究首先通过生物信息学方法分析了TCGA及9个GEO数据库（共10个数据库，其中8个包含EAC数据，6个包含BE数据）中NEK在EAC和BE的表达情况。我们发现与正常食管组织相比，多个NEK成员如NEK2（7/8）、NEK3（6/8）和NEK6（6/8）在EAC中显著上调，而NEK1在EAC中表达下调。相反，这些NEK的基因组改变在EAC中并不常见。我们通过qRT-PCR验证了上述发现，并利用Western blotting检测EAC细胞系中NEK的蛋白表达，同时通过免疫组织化学和免疫荧光技术对原发性EAC组织进行验证。我们的数据表明，NEK2、NEK3和NEK7的频繁上调可能在EAC发展中具有重要作用。
肿瘤(癌症)患者之家