Overexpression of eukaryotic initiation factor 4E (eIF4E) and its clinical significance in lung adenocarcinoma.
BACKGROUND
Eukaryotic initiation factor 4E (eIF4E), an important regulator of translation, plays important roles in tumor transformation, progression and metastasis. However, the clinical significance of eIF4E expression in lung adenocarcinoma (AdC) remains unclear. The aim of this study was to explore the expression of eIF4E gene in lung adenocarcinoma cell lines and tissues, and to investigate its relationship with clinical characteristics and prognosis of patients with lung adenocarcinoma in combination with p53 status.


METHODS
Semi-quantitative RT-PCR and Western blotting assays were performed to detect the expression of eIF4E mRNA and protein in normal human lung epithelial cell line, immortalized lung epithelial cell line and lung adenocarcinoma cell lines. Additionally, the expression of eIF4E gene was also detected in 32 cases of lung adenocarcinoma tissues, tumor adjacent tissues and tumor surrounding normal tissues by the same methods. Moreover, expression of eIF4E and the status of p53 in specimens from 76 patients with lung adenocarcinoma were examined by immunohistochemical staining. Correlations between eIF4E expression and clinicopathological features, and the effect of eIF4E on prognosis of patients with lung adenocarcinoma were evaluated by statistical analysis.


RESULTS
The levels of eIF4E mRNA and protein expression were higher in lung adenocarcinoma cell lines and in telomerase-immortalized lung epithelial cell line than in the normal lung epithelial cell line. The expression of eIF4E gene showed statistical difference between tumor tissues, tumor adjacent tissues and tumor surrounding normal tissues (P<0.05). Moreover, the higher levels of eIF4E expression were correlated with poorer differentiation (P=0.012), higher pathological stage (P<0.0001) and clinical stage (P=0.002), a higher incidence of hematogenous metastasis (P=0.007) and cancer-related death (P=0.036). The 5-year survival rate of patients with higher eIF4E expression was significantly lower than that of patients with lower eIF4E expression (P=0.0045). Furthermore, in a multivariate analysis by Cox regression model, high eIF4E expression was confirmed to be an independent prognostic factor (HR: 2.258; unfavorable, P=0.0056), while lymph node (HR: 2.033; unfavorable, P=0.0440) and hematogenous metastasis (HR: 3.489; unfavorable, P<0.0001) were also significant prognostic factors.


CONCLUSIONS
High eIF4E expression was correlated with poorer overall survival in lung adenocarcinoma patients. eIF4E might be a better clinical marker predicting the prognosis for lung adenocarcinoma patients in combination with p53 status.
Wang
Rui
R
Department of Medical Oncology, Nanjing General Hospital of Nanjing Military Command, PLA, Nanjing 210002, China.
Geng
Jian
J
Wang
Jing-hua
JH
Chu
Xiao-yuan
XY
Geng
Huai-cheng
HC
Chen
Long-bang
LB
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism
D014408:Biomarkers, Tumor; D039561:Eukaryotic Initiation Factor-4E; D012333:RNA, Messenger