Expression of phosphorylated raf kinase inhibitor protein (pRKIP) is a predictor of lung cancer survival

Abstract

BackgroundRaf-1 kinase inhibitor protein (RKIP) has been reported to negatively regulate signal kinases of major survival pathways. RKIP activity is modulated in part by phosphorylation on Serine 153 by protein kinase C, which leads to dissociation of RKIP from Raf-1. RKIP expression is low in many human cancers and represents an indicator of poor prognosis and/or induction of metastasis. The prognostic power has typically been based on total RKIP expression and has not considered the significance of phospho-RKIP.MethodsThe present study examined the expression levels of both RKIP and phospho-RKIP in human lung cancer tissue microarray proteomics technology.ResultsTotal RKIP and phospho-RKIP expression levels were similar in normal and cancerous tissues. phospho-RKIP levels slightly decreased in metastatic lesions. However, the expression levels of phospho-RKIP, in contrast to total RKIP, displayed significant predictive power for outcome with normal expression of phospho-RKIP predicting a more favorable survival compared to lower levels (P = 0.0118); this was even more pronounced in more senior individuals and in those with early stage lung cancer.ConclusionsThis study examines for the first time, the expression profile of RKIP and phospho-RKIP in lung cancer. Significantly, we found that phospho-RKIP was a predictive indicator of survival.

RKIP: Much more than Raf Kinase inhibitory protein

“…The authors demonstrated that patients whose cancers expressed high p‐RKIP levels survived longer than patients with relatively low p‐RKIP expression levels. These data indicate the importance of assessing p‐RKIP and RKIP expression levels to delineate the role of RKIP in different cancers (Huerta‐Yepez et al, 2011). However, although extensive clinical research experiments have indicated that RKIP is an important prognostic and therapeutic target in cancer patients, well‐conducted, randomized clinical trials tailored specifically to early‐stage cancer patients must be employed to determine whether the level of RKIP and/or p‐RKIP in tumor cells may influence prognostication and/or therapy.…”

Reduction of Raf Kinase Inhibitor Protein Expression is Associated with Lymph Node Metastasis in Resectable Non-small Cell Lung Cancer

“…So it is important to find prognostic marker and initiate adjuvant therapy after surgery in these patients. Recent findings demonstrated that phospho-RKIP was a predictive indicator of lung cancer survival [12]. However, there is no research on the relationship of RKIP expression and clinical-pathologic features of surgical lung cancer patients.…”

The presence of Merkel cell polyomavirus is associated with deregulated expression of BRAF and Bcl‐2 genes in non‐small cell lung cancer

“…Mutations of the ras genes, including the K‐ras oncogene, in lung cancer are entirely limited to NSCLC (predominantly adenocarcinoma), whereas in a recent study it has been suggested that the mutant BRAF is a driving “event” in lung adenocarcinoma. Deficiency of the inhibitor RKIP is positively correlated with carcinogenesis as well as invasion and metastasis of lung squamous cell carcinoma, while the total level of RKIP has no predictive value for lung cancer patient outcome . Genotoxic stress results in the activation of the “guardian of the genome” gene p53 .…”