Department of Development of Therapeutic Programs, National Cancer Institute Regina Elena, IRCCS, 00144 Rome, Italy.
J Exp Clin Cancer Res. 2012 Jan 12;31(1):4. doi: 10.1186/1756-9966-31-4.
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. SGK1 is the most represented SGK member.
By 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.
mRNA 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.
This 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.
肺癌是癌症死亡的最常见原因。在非小细胞肺癌(NSCLC)中,只有早期发现和治疗(如果可能),才能显著影响患者的预后。PI3K 信号转导途径在 NSCLC 的恶性肿瘤中起着重要作用,随后 AKT 家族因子被激活。血清和糖皮质激素激酶(SGK)因子与 AKT 因子具有高度的结构和功能同源性,是受细胞应激和激素控制的广泛表达的丝氨酸/苏氨酸激酶家族。SGK1 是最具代表性的 SGK 成员。
通过免疫组织化学和定量实时 PCR,我们在 66 例福尔马林固定、石蜡包埋的 NSCLC 手术样本中测定了 SGK1 蛋白和 mRNA 的表达。所有样本均来自有明确临床病史的患者。
mRNA 表达在鳞状细胞癌中显著升高,与多种临床预后指标相关,在高级别肿瘤、更大肿瘤和更差临床分期的肿瘤中升高。SGK1 蛋白表达与这些临床参数之间没有相关性。
本研究对 NSCLC 样本中 SGK1 表达的探索性分析强调了该因子在 NSCLC 患者预后中的潜在作用。此外,在鳞状细胞癌亚型中的高表达为该 NSCLC 亚型提供了新的治疗可能性,可设计特定的激酶抑制剂。