Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis.
Akt, a downstream mediator of phosphatidylinositol 3-kinase (PI3K), is a signal transduction protein that plays a central role in tumorigenesis. The tumor suppressor gene PTEN negatively regulates the PI3K/Akt signaling pathway. However, the roles of Akt and PTEN function in patients with non-small cell lung cancer (NSCLC) is not well established. To clarify roles of expression of phosphorylated Akt (p-Akt) and loss of PTEN expression in biological behavior and prognosis of NSCLC. Immunohistochemical staining was used to determine the expression of p-Akt and PTEN in 20 cases of normal lung tissues and 102 cases patients with NSCLC. All patients with NSCLC were followed from 3 to 60 months. The positive incidence of p-Akt expression and loss incidence of PTEN expression in NSCLC were 41.2% (42/102) and 46.1% (47/102), while negative of p-Akt expression (0%, 0/20) and positive of PTEN expression (100%, 20/20) in normal lung tissues. Overexpression of p-Akt and loss of PTEN expression were correlated to poor differentiation, lymph node involvement, distant metastasis and late stages. A significant negative correlation was observed between expression of p-Akt and PTEN (r = -0.425, P < 0.001). Patients with p-Akt positive expression (42/102) and loss of PTEN expression (47/102) showed significantly worse 5 years survival rate and median survival time than relevant those with p-Akt negative expression (14.29% versus 33.33%, 14 months versus 32 months, Log-rank test X(2) = 14.24, P < 0.001) and PTEN positive expression (10.64% versus 38.18%, 15 months versus 40 months, Log-rank test X(2) = 21.06, P < 0.001). A univariate analysis revealed that smoking, tumor size, lymph node involvement, distant metastasis, stage, p-Akt and loss of PTEN expression were significant correlative factors with prognosis. The result of multivariate Cox analysis showed that smoking, stage and loss of PTEN expression were independent prognosticators. p-Akt is overexpressed and accompanied by the loss of PTEN in clinical specimens of NSCLC. Both p-Akt and PTEN are concerned with invasion and metastasis of NSCLC. Loss of PTEN expression is an independent poor prognostic factor for patients with NSCLC.
Tang
Jian-Min
JM
Department of Respiratory, Peking University People's Hospital, Xi Cheng District, Beijing, PR China. tjmgrx@yahoo.com.cn
He
Quan-Ying
QY
Guo
Rui-Xia
RX
Chang
Xiu-Jun
XJ
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008168:Lung / Q000737:chemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000032:analysis*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis* / Q000037:antagonists & inhibitors; D015996:Survival Rate
D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C494929:PTEN protein, human