Prognostic value of phospho‐Akt in patients with non‐small cell lung carcinoma: A meta‐analysis

Abstract

Previous studies have been inconsistent with respect to the reported associations between phospho-Akt (p-Akt) overexpression and lung cancer prognosis. In this study, we conducted a systematic review and meta-analysis to assess the prognostic value of p-Akt in patients with non-small cell lung carcinoma (NSCLC). Relevant articles were identified by searching MEDLINE. Hazard risks (HRs) from individual studies were calculated and pooled by using a random-effect model, and heterogeneity and publication bias analyses were also performed. Finally, 18 studies comprising 2,353 patients were included in the metaanalysis. p-Akt overexpression was associated with worse survival in NSCLC patients, and the pooled HRs for all the studies was 1.38 (95% confidence interval [CI]: 1.11-1.70; p < 0.01). After subgroup analysis, the association was strengthened in the surgery treatment group, with an HR of 1.44 (95% CI: 1.19-1.75; p < 0.01), while in the tyrosine kinase inhibitors treatment group, the statistical significance disappeared (HR: 1.22, 95% CI: 0.70-2.14; p 5 0.48). The HR in cases of early stage disease (I-III) was 1.35 (95% CI: 1.08-1.69; p 5 0.04); however, in cases of late stage disease (III-IV), the association became non-significant (HR: 1.22, 95% CI: 0.64-2.33; p 5 0.54). Our results suggest that there was a significantly inverse association between p-Akt overexpression and the prognosis of NSCLC patients, and that this association appeared to be limited in early-stage patients who underwent surgery.Lung cancer is one of the most common malignancies and the leading cause of cancer-related death worldwide.1 Nonsmall cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases, and its 5-year survival rate remains at approximately 17%, despite improvements in cancer therapies over the past few decades.2 Most recently, a number of potential prognostic markers for lung cancer have been identified, including EGFR, k-Ras, p53, ERCC1 and BRCA1.

Vicenin‐2 acts as a radiosensitizer of the non‐small cell lung cancer by lowering Akt expression

“…However, it could not cause any significant reduction in cell viability and pAkt levels when combined with radiation (compared to radiation alone group). Lowering of pAkt level by VCN-2 is important as pAkt is directly correlated to the poor prognosis of NSCLC [60]. Our results corroborated the earlier report since we also observed that VCN-2, alone and in combination with radiation, lowered the levels of Akt (Figs.…”

Kctd20 promotes the development of non‐small cell lung cancer through activating Fak/AKT pathway and predicts poor overall survival of patients

“…Kctd20 has been found to associate with Akt and upregulates its phosphorylation level at Thr308 . The level of phosphorylated Akt, including Thr308 and Ser473, has also been associated with adverse survival of NSCLC patients . However, there are no reports on the prognostic value of Kctd20.…”

Characterisation of the Phosphatidylinositol 3-Kinase Pathway in Non-Small Cell Lung Cancer Cells Isolated from Pleural Effusions

“…Interestingly, p-AKT levels were associated with adverse survival in a univariate but not a multivariate analysis. The sample could be the limiting factor as p-AKT levels have been previously shown to be associated with survival in NSCLC; however, the results are not consistent [25,27,30]. …”

“…Several groups have investigated the activation of the PI3K pathway in NSCLC by focusing on levels of p-AKT as a marker of pathway activation. Results were obtained using immunohistochemical techniques in the majority of cases [25,26,27,28], while the prognostic role of p-AKT overexpression still remains unclear [29,30]. Immunohistochemistry techniques studying phosphoproteins are challenging to quantify accurately, while de-phosphorylation may occur ex vivo before fixation due to the instability of phosphoepitopes [31].…”