Background: It has been proven that ornithine aminotransferase (OAT) might play an important role in the oncogenesis and progression of numerous malignant tumors. The aim of this study is to detect the mRNA and protein expression of OAT in non-small cell lung cancer (NSCLC), as well as to analyze the bioinformatic features and binary interactions.
Methods: OAT mRNA expression was detected in A549 and 16HBE cell lines by reverse transcription-polymerase chain reaction. OAT protein expression was determined in 55 cases of NSCLC and 17 cases of adjacent non-tumor lung tissues by immunohistochemical staining. The bioinformatic features and binary interactions of OAT were analyzed. Gene ontology annotation and signal pathway analysis were performed.
Results: OAT mRNA expression in A549 cells was 2.85-fold lower than that in 16HBE cells. OAT protein expression was significantly higher in NSCLC tissues than that in adjacent non-tumor lung tissues. A significant difference of OAT protein expression was existed between squamous cell lung cancer and adenocarcinoma (P < 0.05), but was not correlated with the gender, age, lymph node metastasis, tumor size, and TNM stages. Bioinformatic analysis suggested that OAT was a highly homologous and stable protein located in the mitochondria. An aminotran-3 domain and several sites of phosphorylation, which may function in signal transduction, gene transcription, and molecular transit, were found. In the 54 selected binary interactions of OAT, TNF and TRAF6 play roles in the NF-κB pathway.
Conclusions: OAT may play an important role in the oncogenesis and progression of NSCLC. Thus, OAT may be a novel biomarker for the diagnosis of NSCLC or a new target for its treatment.
背景与目的: 已有的研究表明，鸟氨酸氨基转移酶（ornithine aminotransferase, OAT）可能参与多种恶性肿瘤的发生和发展，本研究旨在检测非小细胞肺癌（non-small cell lung cancer, NSCLC）中OAT mRNA和蛋白质的表达，并对其进行生物信息学分析。
方法: 通过RT-PCR的方法比较A549和16HBE细胞间OAT mRNA水平的差异；采用免疫组织化学SP法检测55例肺癌组织和17例癌旁肺组织中OAT蛋白表达；利用生物信息学的方法对OAT蛋白的生物信息学特征和相互作用蛋白进行分析，并对筛选出来的相互作用蛋白进行GO注释和信号通路分析。
结果: ① A549中OAT mRNA相对含量较16HBE中低，两者差异约2.85倍。②NSCLC中OAT蛋白的表达明显高于癌旁肺组织（P < 0.05）；OAT蛋白在鳞癌和腺癌间的表达差异有统计学意义，而与患者性别、年龄、有无淋巴结转移、肿瘤直径及TNM分期无关。③生物信息学分析提示OAT蛋白定位于线粒体、为高度保守的亲水性蛋白，具有Aminotran-3结构域，可能存在多个丝/苏氨酸磷酸化位点，在信号转导、转录和分子转运等方面发挥一定的作用；在筛选出来的54种可能和OAT存在相互作用的蛋白质中，TNF和TRAF6这两种蛋白参与了NF-κB信号通路。
结论: OAT可能在NSCLC的发生和发展中发挥重要作用，有望成为肺癌的早期诊断标志物和治疗的新靶点。