Let-7g and miR-21 expression in non-small cell lung cancer: Correlation with clinicopathological and molecular features

Abstract

Abstract. MicroRNAs (miRNAs) play a key role in cancer pathogenesis and are involved in several human cancers, including non-small cell lung cancer (NSCLC). This study evaluated Let-7g and miR-21 expression by quantitative realtime PCR in 80 NSCLC patients and correlated the results with their main clinicopathological and molecular features. MiR-21 expression was significantly higher in NSCLC tissues compared to non-cancer lung tissues (p<0.0001), while no significant changes in Let-7g expression were observed between the tumor and normal lung tissues. Target prediction analysis led to the identification of 26 miR-21 and 24 Let-7g putative target genes that play important roles in cancer pathogenesis and progression. No significant association was observed between the analysed miRNAs and the main clinicopathological or molecular characteristics of the NSCLC patients, although both miRNAs were downregulated in squamous cell carcinomas compared to adenocarcinomas. Noteworthy, we observed a significant association between low Let-7g expression and metastatic lymph nodes at diagnosis (p=0.046), as well as between high miR-21 expression and K-Ras mutations (p=0.0003). Survival analysis did not show any significant correlation between prognosis and the analysed miRNAs, although the patients with a high Let-7g and miR-21 expression showed a significantly lower short-term progression-free survival (p=0.01 and p=0.0003, respectively) and overall survival (p=0.023 and p=0.0045, respectively). In conclusion, we showed that Let-7g and miR-21 expression was deregulated in NSCLC and we demonstrated a strong relationship between miR-21 overexpression and K-Ras mutations. Our data indicate that Let-7g and miR-21 profiling combined with the determination of K-Ras mutational status may be considered a useful biomarker for a more effective molecular characterization and clinical management of NSCLC patients. IntroductionLung cancer is the leading cause of cancer-related mortality worldwide (1) and 85% of the cases are represented by nonsmall cell lung cancer (NSCLC), which is classified into three different histological subtypes: adenocarcinoma (ADC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC) (2-4). Despite a better understanding of the NSCLC pathogenesis and significant improvement in early diagnosis and treatment, the overall 5-year survival is extremely low (~15%) and the patients show high recurrence rates even at the early disease stages (1-7), highlighting the necessity of a deeper knowledge of NSCLC biology and the identification of more effective biomarkers.MicroRNAs (miRNAs) are a highly conserved family of small (17-22 nucleotides), non-coding, endogenous, singlestranded RNA molecules that negatively regulate gene expression by binding to complementary sequences on target messenger RNA (mRNA) (8,9). Recently, miRNAs have been shown to regulate essential cell processes, such as cell proliferation, differentiation, apoptosis, development and metabolism (9-11), and to play a key role in cancer pathogenesi...

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