Stojsic Jelena, Stankovic Tijana, Stojkovic Sonja, Milinkovic Vedrana, Dinic Jelena, Milosevic Zorica, Milovanovic Zorka, Tanic Nikola, Bankovic Jasna
Department of Thoracopulmonary Pathology Service of Pathology, Clinical Centre of Serbia, Koste Todorovica 20/26, 11000 Belgrade, Serbia.
Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
Exp Mol Pathol. 2015 Feb;98(1):27-32. doi: 10.1016/j.yexmp.2014.11.010. Epub 2014 Nov 20.
Lung cancer is the most common cause of neoplasia-related death worldwide. Accounting for approximately 80% of all lung carcinomas, the non-small cell lung carcinoma (NSCLC) is the most common clinical form with its two predominant histological types, adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although surgical resection is the most favorable treatment for patients with NSCLC, relapse is still high, so neoadjuvant chemotherapy (NAC) is an accepted treatment modality. In this study we examined whether some of the key molecules associated with the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways could have predictive and prognostic value for the NAC application. To that end we examined the expression status of PTEN, pAKT, pERK and loss of heterozygosity (LOH) of PTEN in two groups of NSCLC patients, those who received and those who did not receive NAC. LOH PTEN and low pERK expression is shown to be correlated with the longest survival of patients with SCC and ADC, respectively, who received NAC. These results point that the application of NAC is beneficial in the NSCLC patients with specific molecular alterations which could further help to improve constant search for the druggable molecular targets used in personalized therapy.
肺癌是全球范围内肿瘤相关死亡的最常见原因。非小细胞肺癌（NSCLC）约占所有肺癌的80%，是最常见的临床类型，主要有两种组织学类型，即腺癌（ADC）和鳞状细胞癌（SCC）。尽管手术切除是NSCLC患者最有利的治疗方法，但复发率仍然很高，因此新辅助化疗（NAC）是一种被认可的治疗方式。在本研究中，我们检测了一些与RAS/RAF/MEK/ERK和PI3K/AKT/mTOR信号通路相关的关键分子是否对NAC的应用具有预测和预后价值。为此，我们检测了两组NSCLC患者（接受NAC和未接受NAC的患者）中PTEN、pAKT、pERK的表达状态以及PTEN的杂合性缺失（LOH）情况。结果显示，PTEN的LOH和低pERK表达分别与接受NAC的SCC和ADC患者的最长生存期相关。这些结果表明，NAC应用于具有特定分子改变的NSCLC患者是有益的，这可能进一步有助于改进对用于个性化治疗的可成药分子靶点的持续探索。
