Abstract:
Eukaryotic elongation factor 1 alpha 2 (eEF1A2) encodes an isoform of the alpha subunit of the elongation factor 1 complex and is responsible for the enzymatic delivery of aminoacyl tRNA to the ribosome. Our proteomic analysis has identified eEF1A2 as one of the proteins expressed during malignant progression from adenocarcinoma in situ (AIS) to early invasive lung adenocarcinoma. The expression level of eEF1A2 in 175 lung adenocarcinomas was examined by immunohistochemical staining in relation to patient prognosis and clinicopathological factors. Quantitative PCR analysis and fluorescence in situ hybridization (FISH) were performed to evaluate the amplification of the eEF1A2 gene. Relatively high expression of eEF1A2 was observed in invasive adenocarcinoma (39/144 cases) relative to minimally invasive adenocarcinoma (1/10 cases) or AIS (0/21 cases). Among invasive adenocarcinomas, solid-type adenocarcinoma (15/32 cases, 47%) showed higher expression than other histological subtypes (23/92, 25%). Patients with eEF1A2-positive tumors had a significantly poorer prognosis than those with eEF1A2-negative tumors. Of the five tumors that were eEF1A2-positive, two cases showed amplified genomic eEF1A2 DNA, which was confirmed by both qPCR and FISH. These findings indicate that eEF1A2 overexpression occurs in the course of malignant transformation of lung adenocarcinomas and is partly due to eEF1A2 gene amplification.
摘要:
真核延伸因子1α2(eEF1A2)编码延伸因子1复合物的α亚基的同种型,并负责将氨酰基tRNA酶促递送到核糖体。我们的蛋白质组学分析已经确定eEF1A2是在从原位腺癌(AIS)到早期浸润性肺腺癌的恶性进展过程中表达的蛋白质之一。通过免疫组织化学染色检查了175例肺腺癌中eEF1A2的表达水平与患者预后和临床病理因素的关系。进行定量PCR分析和荧光原位杂交(FISH)以评估eEF1A2基因的扩增。eEF1A2在浸润性腺癌(39/144例)中的表达相对于微创性腺癌(1/10例)或AIS(0/21例)较高。在侵袭性腺癌中,实型腺癌(15/32例,47%)显示表达高于其他组织学亚型(23/92,25%)。eEF1A2阳性肿瘤患者的预后明显低于eEF1A2阴性肿瘤患者。在五个eEF1A2阳性的肿瘤中,两例显示扩增的基因组eEF1A2DNA,qPCR和FISH都证实了这一点。这些发现表明,eEF1A2过表达发生在肺腺癌的恶性转化过程中,部分原因是eEF1A2基因扩增。