Prognostic significance of twist and N-cadherin expression in NSCLC.

Linping Hui,Dali Tian,Zeshi Cui,Xueshan Qiu,Siyang Zhang,Xinjun Dong,Sai Yendamuri

doi:10.1371/journal.pone.0062171

Abstract

BackgroundMetastasis is the most common cause of disease failure and mortality for non-small cell lung cancer after surgical resection. Twist has been recently identified as a putative oncogene and a key regulator of carcinoma metastasis. N-cadherin is associated with a more aggressive behavior of cell lines and tumors. The aim of this study was to evaluate the clinical relevance of Twist and N-cadherin expression in NSCLC, and the effects of Twist1 knockdown on lung cancer cells.MethodsWe examined the expressions of Twist and N-cadherin by immunohistochemistry in 120 cases of non-small cell lung cancer (including 68 cases with follow-up records). We also analyzed Twist1 and N-cadherin mRNA expression in 30 non-small cell lung cancer tissues using quantitative reverse transcription polymerase chain reaction. The functional roles of Twist1 in lung cancer cell lines were evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell apoptosis and invasion.ResultsIn lung cancer tissues, the overexpression rate of Twist was 38.3% in lung cancer tissues. Overexpression of N-cadherin was shown in 40.83% of primary tumors. Moreover, Twist1 mRNA expression levels correlated with N-cadherin mRNA levels. Furthermore, overexpression of Twist1 or N-cadherin in primary non-small cell lung cancers was associated with a shorter overall survival (P<0.01, P<0.01, respectively). Depleting Twist expression inhibited cell invasion and increased apoptosis in lung cancer cell lines.ConclusionsThe overexpression of Twist and N-cadherin could be considered as useful biomarkers for predicting the prognosis of NSCLC. Twist1 could inhibit apoptosis and promote the invasion of lung cancer cells, and depletion of Twist1 in lung cancer cells led to inhibition of N-cadherin expression.

Highlights

Lung cancer is a common malignancy, which causes millions of deaths worldwide every year
We examined the expression of N-cadherin in serial sections (Figure 1)
A multivariate analysis demonstrated that Ncadherin overexpression and Twist/N-cadherin co-overexpression were significant predictors of survival (Table 2)

Summary

Introduction

Lung cancer is a common malignancy, which causes millions of deaths worldwide every year. The failure of NSCLC therapy and poor prognosis of the disease are mostly attributed to the development of local and distant metastases [4]. In this regard, the acquisition of new therapeutic targets that play important roles in pulmonary carcinogenesis, progression and metastasis will be essential for improving therapeutic intervention and prognosis of lung cancers. Metastasis is the most common cause of disease failure and mortality for non-small cell lung cancer after surgical resection. The aim of this study was to evaluate the clinical relevance of Twist and N-cadherin expression in NSCLC, and the effects of Twist knockdown on lung cancer cells

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