Expression of STAT5, COX-2 and PIAS3 in correlation with NSCLC histhopathological features.

Abstract

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.

• Authors: Dorota Pastuszak-Lewandoska, Daria Domańska, Karolina H Czarnecka, Jacek Kordiak, Monika Migdalska-Sęk, Ewa Nawrot, Justyna Kiszałkiewicz, Adam Antczak, Paweł Górski, Ewa Brzeziańska
• Journal: PloS one (PLoS One) Vol. 9 Issue 8 Pg. e104265 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25137041 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Molecular Chaperones
• PIAS3 protein, human
• Protein Inhibitors of Activated STAT
• Protein Isoforms
• RNA, Messenger
• STAT5 Transcription Factor
• Cyclooxygenase 2
• PTGS2 protein, human

Topics

• Aged
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology)
• Cell Transformation, Neoplastic (genetics, metabolism, pathology)
• Cyclooxygenase 2 (genetics, metabolism)
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Lymphatic Metastasis
• Male
• Middle Aged
• Molecular Chaperones (genetics, metabolism)
• Neoplasm Staging
• Protein Inhibitors of Activated STAT (genetics, metabolism)
• Protein Isoforms (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Risk Factors
• STAT5 Transcription Factor (genetics, metabolism)
• Smoking (physiopathology)