Pastuszak-Lewandoska Dorota, Domańska Daria, Czarnecka Karolina H, Kordiak Jacek, Migdalska-Sęk Monika, Nawrot Ewa, Kiszałkiewicz Justyna, Antczak Adam, Górski Paweł, Brzeziańska Ewa
Department of Molecular Bases of Medicine, Medical University of Lodz, Lodz, Poland.
Department of Chest Surgery, General and Oncological Surgery, University Hospital No. 2, Medical University of Lodz, Lodz, Poland.
PLoS One. 2014 Aug 19;9(8):e104265. doi: 10.1371/journal.pone.0104265. eCollection 2014.
Signal transducers and activators of transcription (STATs), their inhibitors and cyclooxygenase-2 (COX-2) participate in transformations of many various types of cancers. The aim of the present study was to evaluate the relationship between STAT5A/B, COX-2, and PIAS3 mRNA expression and tumor staging, metastasis status, and histopathological subtype in 71 patients with confirmed non-small cell lung cancer (NSCLC) diagnosis. Total RNA was isolated from NSCLC tissue samples and the expression of the studied genes was assessed using TaqMan probes in real-time PCR assay. The expression levels of STAT5A, STAT5B, and COX-2 genes were increased in 69%, 79%, and 71% NSCLC samples respectively, while PIAS3 expression was decreased in the majority (69%) of the studied tissues. Statistically significant differences were observed between STAT5 isoforms (P = 0.0008), with higher expression of STAT5B. We found statistically significant positive correlation between STAT5B and COX-2 (rho = 0.045), and significant negative correlation between STAT5B and PIAS3 (rho = -0.049). The negative correlation between STAT5B and PIAS3 (rho = -0.43) was also observed in T2a+T2b tumor group. Additionally, STAT5B and COX-2 expression levels were significantly different between T1a+T1b and T2a+T2b tumors (P = 0.002 and P = 0.041, respectively), with higher expression of both genes in T2 tumor stage. PIAS3 expression was significantly lower in NSCC subtype as compared with SCC subtype (P = 0.017). Also, STAT5A and STAT5B immunoexpression was assessed, and the results indicated significantly higher protein levels in NSCLC patients as compared with controls (P = 0.048 and P = 0.034, respectively). High STAT5B immunoexpression was positively correlated with STAT5B gene expression in tumors (rho = 0.755). STAT5B protein level was also significantly higher in T2a+T2b tumors, reflecting high STAT5B gene expression in this group. There was no statistically significant association between mRNA and protein expression levels of the studied genes and patients' characteristics: age, gender, smoking. The obtained results highlight the importance of the genes STAT5B and COX-2 in lung cancer progression.
信号转导和转录激活因子(STATs)、其抑制剂以及环氧合酶-2(COX-2)参与多种类型癌症的转变过程。本研究旨在评估71例确诊为非小细胞肺癌(NSCLC)患者中STAT5A/B、COX-2和PIAS3 mRNA表达与肿瘤分期、转移状态及组织病理学亚型之间的关系。从NSCLC组织样本中分离总RNA,并使用TaqMan探针通过实时PCR测定法评估所研究基因的表达。在NSCLC样本中,STAT5A、STAT5B和COX-2基因的表达水平分别在69%、79%和71%的样本中升高,而在所研究的大多数组织(69%)中PIAS3表达降低。在STAT5异构体之间观察到统计学上的显著差异(P = 0.0008),STAT5B表达较高。我们发现STAT5B与COX-2之间存在统计学上的显著正相关(rho = 0.045),而STAT5B与PIAS3之间存在显著负相关(rho = -0.049)。在T2a + T2b肿瘤组中也观察到STAT5B与PIAS3之间的负相关(rho = -0.43)。此外,T1a + T1b和T2a + T2b肿瘤之间STAT5B和COX-2的表达水平存在显著差异(分别为P = 0.002和P = 0.041),这两个基因在T2肿瘤分期中的表达均较高。与鳞状细胞癌(SCC)亚型相比,NSCC亚型中PIAS3表达显著较低(P = 0.017)。此外,还评估了STAT5A和STAT5B的免疫表达,结果表明NSCLC患者的蛋白水平显著高于对照组(分别为P = 0.048和P = 0.034)。肿瘤中高STAT5B免疫表达与STAT5B基因表达呈正相关(rho = 0.755)。T2a + T2b肿瘤中STAT5B蛋白水平也显著较高,反映了该组中STAT5B基因的高表达。所研究基因的mRNA和蛋白表达水平与患者特征(年龄、性别、吸烟)之间无统计学上的显著关联。所得结果突出了STAT5B和COX-2基因在肺癌进展中的重要性。