The prognostic value of altered eIF3a and its association with p27 in non-small cell lung cancers.
BACKGROUND
Over-expressed eukaryotic initiation factor 3a (eIF3a) in non-small cell lung cancer (NSCLC) contributed to cisplatin sensitivity. However, the role of eIF3a in oncogenesis was still controversial. This study was designed to investigate the prognostic impact of eIF3a and p27 in radically resected NSCLC patients.


METHODS
The expression levels of subcellular eIF3a and p27 were evaluated immunohistochemically in 537 radically resected NSCLC samples, and another cohort of 210 stage II NSCLC patients. Disease specific survival (DSS) and disease free survival (DFS) were analyzed by Kaplan-Meier method and Cox regression model.


RESULTS
The subcellular expression of eIF3a was strongly correlated with status of p27 (Spearman rank coefficient correlation for cytoplasmic eIF3a and p27=0.653, for nuclear staining=0.716). Moreover, survival analysis revealed favorable prognostic impact of nuclear eIF3a, p27, and the combination high nuclear staining on NSCLC (Hazards Ratio=0.360, 95%CI=0.109-0.782, P=0.028). In addition, interaction research between biomarkers and chemotherapy status disclosed cisplatin-based regimen trend to prolong DSS of stage II NSCLC patients with high eIF3a-C (P=0.036)and low p27-N (P=0.031).


CONCLUSIONS
Our findings suggested altered eIF3a expression closely correlated with p27 status, and the association was of prognostic value for resected NSCLC. Altered expression of eIF3a and p27 predicted prognosis of NSCLC independently.
Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 8, P. R. China; Department of Clinical Pharmacy, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, P. R. China.
Jie
J
Shen
Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 8, P. R. China.
Ji-Ye
JY
Yin
Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 8, P. R. China.
Xiang-Ping
XP
Li
Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 8, P. R. China.
Zhao-Qian
ZQ
Liu
Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 8, P. R. China.
Ying
Y
Wang
Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 8, P. R. China.
Juan
J
Chen
Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 8, P. R. China.
Jian
J
Qu
Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 8, P. R. China.
Xiao-Jing
XJ
Xu
Personalized Medicine Institute, Moffitt Cancer Center, Tampa, Florida, United States of America.
Howard Lewis
HL
McLeod
Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 8, P. R. China.
Yi-Jing
YJ
He
State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, P. R. China.
Kun
K
Xia
Department of Clinical Pharmacy, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, P. R. China.
Yuan-Wei
YW
Jia
Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 8, P. R. China.
Hong-Hao
HH
Zhou
D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis
C105988:EIF3A protein, human; D039621:Eukaryotic Initiation Factor-3; D050760:Cyclin-Dependent Kinase Inhibitor p27