Abstract
BackgroundLung cancer represents the most frequent cause of death for cancer. In non-small cell lung cancer (NSCLC), which accounts for the vast majority of this disease, only early detection and treatment, when possible, may significantly affect patient's prognosis. An important role in NSCLC malignancy is attributed to the signal transduction pathways involving PI3Kinase, with consequent activation of the AKT family factors. The serum and glucocorticoid kinase (SGK) factors, which share high structural and functional homologies with the AKT factors, are a family of ubiquitously expressed serine/threonine kinases under the control of cellular stress and hormones. SGK1 is the most represented SGK member.MethodsBy means of immunohistochemistry and quantitative real-time PCR, we determined SGK1 protein and mRNA expression in a cohort of 66 formalin-fixed, paraffin-embedded NSCLC surgical samples. All samples belonged to patients with a well-documented clinical history.ResultsmRNA expression was significantly higher in squamous cell carcinomas, and correlated with several clinical prognostic indicators, being elevated in high-grade tumors and in tumors with bigger size and worse clinical stage. No correlation was found between SGK1 protein expression and these clinical parameters.ConclusionsThis explorative analysis of SGK1 expression in NSCLC samples highlights the potential role of this factor in NSCLC patients' prognosis. Moreover, the higher expression in the squamous cell carcinoma subtype opens new therapeutic possibilities in this NSCLC subtype by designing specific kinase inhibitors.
Highlights
Lung cancer represents the most frequent cause of death for cancer
SGK1 mRNA detection in non-small cell lung cancer (NSCLC) samples By means of the specific primers illustrated in Table 1, we determined the mRNA amount of SGK1 either as the sum of the four different splicing variants or as the value specific for each single variant
As far as it concerns the evaluation of the expression of the sum of the four SGK1 mRNA, statistically significant correlation was found with: a) histolopathogical subtype (P = 0.022), with the highest expression in squamous cell carcinomas; b) histopathological grade (P = 0.026), with the lowest expression in low-grade tumors (G1) and the highest expression in high-grade tumors (G3); c) tumor size (P = 0.013), with lower expression in T1 and higher in T3-T4 tumors
Summary
Lung cancer represents the most frequent cause of death for cancer. In non-small cell lung cancer (NSCLC), which accounts for the vast majority of this disease, only early detection and treatment, when possible, may significantly affect patient’s prognosis. An important role in NSCLC malignancy is attributed to the signal transduction pathways involving PI3Kinase, with consequent activation of the AKT family factors. The serum and glucocorticoid kinase (SGK) factors, which share high structural and functional homologies with the AKT factors, are a family of ubiquitously expressed serine/threonine kinases under the control of cellular stress and hormones. A pivotal step of the cascade triggered by tyrosine kinase receptors is the activation of the phosphoinositide-3-kinase (PI3Kinase) pathway, which allows the convergence of several signals in activating the AKT family of serine/threonine kinases, stimulating cell growth, mitosis, survival and energy metabolism [12,13,14]. SGK1, the most represented member of the SGK family, is ubiquitously expressed and is under the control of cellular stress (including cell shrinkage) and hormones (including gluco-and mineral-corticoids). All isoforms are activated by insulin and other growth factors [15]
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