High expression of eukaryotic elongation factor 1-alpha-2 in lung adenocarcinoma is associated with poor prognosis

被引:1
作者
Yamato, Mariko [1 ,2 ]
Dai, Tomoko [2 ,3 ]
Murata, Yoshihiko [1 ,2 ]
Nakagawa, Tomoki [1 ,2 ]
Kikuchi, Shinji [4 ,5 ]
Matsubara, Daisuke [1 ,2 ]
Noguchi, Masayuki [3 ,6 ]
机构
[1] Univ Tsukuba Hosp, Dept Pathol, Ibaraki, Japan
[2] Univ Tsukuba, Dept Diagnost Pathol, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan
[3] Shonan Kamakura Gen Hosp, Ctr Clin & Translat Sci, Kamakura, Japan
[4] Univ Tsukuba, Fac Med, Dept Thorac Surg, Tsukuba, Ibaraki, Japan
[5] Ibaraki Cent Hosp, Dept Thorac Surg, Ibaraki, Japan
[6] Narita Tomisato Tokushukai Hosp, Dept Pathol, Chiba, Japan
基金
日本学术振兴会;
关键词
adenocarcinoma in situ (AIS); clinicopathological analysis; gene amplification; immunohistochemistry; lung adenocarcinoma; FACTOR EEF1A2; CANCER CELLS; FACTOR-1-ALPHA; GENE; OVEREXPRESSION; APOPTOSIS; ONCOGENE; PROFILES; INVASION; AKT;
D O I
10.1111/pin.13457
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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. The expression level of eEF1A2 in 175 lung adenocarcinomas was examined using immunohistochemistry. Relatively high expression of eEF1A2 was observed in invasive adenocarcinoma relative to MIA or AIS. Among invasive adenocarcinomas, solid-type adenocarcinoma showed higher expression than other histological subtypes. qPCR and FISH analyses demonstrated an increase of genomic eEF1A2 DNA in specimens of invasive adenocarcinoma. These findings indicate that eEF1A2 overexpression occurs in the course of malignant transformation of lung adenocarcinomas and is partly due to eEF1A2 gene amplification. image
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页码:454 / 463
页数:10
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