비소세포 폐암 환자 조직에서 microRNAs와 열충격단백질90 계의 발현과 임상병리학적 특성과의 상관관계

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that exert a critical influence on tumorigenesis through post-transcriptional modification and are considered to be potential biomarkers for the diagnosis or prognosis of various cancers. Although several miRNAs have been proposed as relevant biomarkers for non-small cell lung cancer (NSCLC), detailed working mechanisms and validated prognostic significance of these miRNAs remain controversial. Heat shock protein 90 (HSP90), a molecular chaperone, plays important roles in cellular protection against various stressful stimuli and in the regulation of cellular growth and apoptosis. In the present study, we evaluated the expression levels of miRNA-126, miRNA-155 and miRNA-200c in 72 NSCLCs and 30 benign lung tissues by real time quantitative reverse transcription PCR (RT-qPCR) and analyzed the correlation of miRNAs expression with a variety of clinicopathological factors and patient survival. In addition, we assessed the differential expression of HSP90 family proteins in non-small cell lung cancer (NSCLC) and the correlation of their expression levels with clinicopathological factors and patient survival rates. Result of this study were summarized as follows; 1. The ΔCt values of RT-qPCR showed that miRNA-155 and miRNA-200c expressions were significantly upregulated in NSCLCs (p<0.001), while miRNA-126 expression was significantly downregulated in NSCLCs (p<0.001). 2. The expression of miRNA-126 was significantly higher in NSCLCs with a tumor size of ≤3 cm than in those with a tumor size of >3 cm (p=0.026). Over expression of miRNA-155 was significantly associated with lymph node metastasis and poor differentiation (p=0.046). There were no other significant associations between miRNA expression and clinicopathological features. In survival analysis for all NSCLC patients, high miRNA-155 expression (p=0.048) and high miR-200c expression (p=0.037) were significantly correlated with lower overall survival. 3. HSP90α showed higher expression in patients with no lymphovascular invasion (p=0.014). HSP90β showed higher expression in squamous cell carcinoma (p=0.003) and over expression of GRP94 was significantly associated with poor differentiation (p=0.048). However, none of the HSP90 proteins showed significant associations with survival status in patients with NSCLC. My results suggest that miRNA-126 might play a role in tumor-suppressive and miRNA-155 and miRNA-200c in an oncogenic role, and these miRNAs are potential prognostic biomarkers for NSCLC. My results also indicate that HSP90α might contribute more to the carcinogenesis of NSCLC than those of HSP90β and GRP94 and that isoform selectivity should be considered when HSP90 inhibitors are studied or utilized for the treatment of NSCLC.