Prognostic Significance of 14-3-3γ Overexpression in Advanced Non-Small Cell Lung Cancer

Abstract

The 14-3-3 protein has been shown to be involved in the cancer process. However, there is no understanding of the relationship between 14-3-3γ (14-3-3 gamma) expression and prognosis in advanced non-small cell lung cancer. In this study, we therefore investigated the association between protein levels by immunohistochemistry and clinicopathological features of advanced NSCLC patients. Survival curves were estimated using the Kaplan-Meier method and tested by log-rank. Multivariate analysis was conducted with the Cox's regression model to determine independence of factors. p values less than 0.05 were considered significant. A total 153 patients were studied, with 54.3% being stage III and 45.8% stage IV. Fifty-one cases (33.3%) were squamous cell carcinomas, and 98 cases (64.1%) were adenocarcinomas. High 14-3-3γ expression was seen in 59.5% and significantly correlated with lymph node metastasis (p=0.010) and distant metastasis (p=0.017). On Kaplan-Meier analysis, high 14-3-3γ expression was associated with poorer survival with a marginal trend toward significance (p=0.055). On multivariate analysis, age, treatment, and 14-3-3γ expression proved to be independent prognostic parameters. In vitro experiments indicated that 14-3-3γ overexpression also played a potential role in cancer invasion. In conclusion, our data suggest that 14-3-3γ overexpression is associated with invasion and a poor prognosis. Therefore, 14-3-3γ may be a potential prognostic marker of advanced non-small cell lung cancer.

Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma patients

“…Of these 442 proteins, 102 ( t ‐test <0·05) and 20 (B‐H adjusted t ‐test P < 0·05) proteins were differentially expressed between the two patient groups (all 102 are listed in Table SII) (Fig ). Sixty‐five proteins were overexpressed in the REF/REL group and several of these proteins (Elongation factor 1‐beta, 14‐3‐3 protein gamma, nucleophosmin 1, RAP1B, Heat shock protein 60 and IMP dehydrogenase 2) have previously been described as negative prognostic factors or involved in drug resistance in other malignancies (De Bortoli et al , ; Li et al , ; Raungrut et al , ; Zhou et al , ; Yang et al , ; Sawazaki et al , ). Two proteins overexpressed in the REF/REL group have been reported as a negative prognostic marker or associated with multidrug resistance in DLBCL: Y‐box protein 1 (Miao et al , ) and pontin/RuvBL1 protein (Nishiu et al , ).…”

Long non‑coding RNA HOX transcript antisense RNA promotes expression of 14‑3‑3σ in non‑small cell lung cancer

“…14-3-3 proteins are a family of highly conserved proteins comprised of at least seven isoforms in mammalian cells (4). Overexpression of the 14-3-3 isoforms β, γ, σ and θ has been identified in lung cancer (12).…”

“…Therefore, studies into novel therapeutic targets and strategies to treat patients with NSCLC are warranted. The 14-3-3 protein family consists of at least seven isoforms, namely β, ε, γ, η, σ, τ/θ and ξ, which are found in mammalian cells (4). A number of important signaling events, including cell proliferation and survival are regulated by 14-3-3 proteins (5,6).…”

“…Overexpression of 14-3-3 proteins has been detected in many types of human cancer such as pancreatic cancer (8), lung adenocarcinoma (9), breast tumor (10) and is correlated with more aggressive tumors and poor prognosis (10,11). In lung cancer, it has been demonstrated that the 14-3-3 isoforms β, γ, σ and θ are overexpressed in tumor tissue compared with normal tissues (4,12). Among these, 14-3-3σ has been indicated to be elevated in NSCLC as a result of 14-3-3σ DNA hypomethylation (13).…”

Integrate Omics Data and Molecular Dynamics Simulations toward Better Understanding of Human 14-3-3 Interactomes and Better Drugs for Cancer Therapy

“…Knockdown of gamma isoform of 14-3-3 by siRNA treatment led to significantly diminished metastasis rates in non-small cell lung cancer cells (Raungrut et al, 2014).…”