Open AccessPrognostic impact of R af‐1 and p‐ R af‐1 expressions for poor survival rate in non‐small cell lung cancer
Author(s) -
Qiu ZhiXin,
Wang Lei,
Han Juan,
Liu Dan,
Huang Wei,
Altaf Kiran,
Qiu XueSong,
Javed Muhammad A.,
Zheng Jing,
Chen BoJiang,
Li WeiMin
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02375.x
Subject(s) - lung cancer , carcinogenesis , medicine , immunohistochemistry , adenocarcinoma , cancer research , survival rate , survival analysis , in vivo , apoptosis , oncology , proportional hazards model , a549 cell , carcinoma , cancer , biology , biochemistry , microbiology and biotechnology
Overexpression of R af‐1 has commonly been observed in solid tumors including non‐small cell lung cancer ( NSCLC ). The objective of this study was to investigate whether overexpression of R af‐1, phosphorylated‐ R af‐1 (p‐ R af‐1) or both correlates with poor survival rate in NSCLC patients and to explore associations between expression of these proteins and NSCLC cell fate both in vitro and in vivo . Expression of R af‐1 and p‐ R af‐1 were detected by immunohistochemistry in tumor specimens from 152 NSCLC patients and associations between their expression and the clinicopathological characteristics were assessed. Five‐year median survival rate of patients were analyzed by K aplan– M eier method, log‐rank test and C ox regression. Cell fate was compared between normal tumor cells and those with R af‐1 silencing, in both the adenocarcinoma cell line A 549 and xenografted mice that were infected with the A 549 cell line. The incidence of overexpression of both R af‐1 and p‐ R af‐1 in NSCLC was much higher than normal control ( P < 0.05), and the survival rate of patients with positive expression of R af‐1, p‐ R af‐1 or both was found to be significantly lower than the negative group ( P < 0.05). Both univariate and multivariate analyses showed R af‐1 ( P = 0.000, P = 0.010), p‐ R af‐1 ( P = 0.004, P = 0.046), or both ( P = 0.001, P = 0.016) was good prognostic markers for poor survival rate in NSCLC patients. Suppression of R af‐1 inhibited tumorigenesis by inducing apoptosis both in vitro and in vivo . These findings demonstrate that overexpression of R af‐1, p‐ R af‐1 or both could be considered as a new independent prognostic biomarker for poor survival rates for NSCLC patients.