Comparison of cofilin-1 and Twist-1 protein expression in human non-small cell lung cancer tissues

摘要

Metastasis is the primary cause of mortality in patients with non-small cell lung cancer (NSCLC). Actin cytoskeletal reorganization is usually accompanied by the epithelial-mesenchymal transition (EMT)-induced invasion and metastasis of cancer cells. In the present study, expression levels of the actin-associated protein cofilin-1 and of the pivotal EMT molecule Twist-1 were determined in NSCLC tissues. Using lung cancer tissue arrays, the identification of 67.4% of tissue spots that exhibited reciprocal levels of cofilin-1 and Twist-1 was achieved by immunohistochemical (IHC) staining. This reciprocal expression pattern was also detected in 21 out of 25 clinicopathological NSCLC tissue sections, and in 10 out of 15 NSCLC cell lines. In addition, high levels of cofilin-1 and low levels of Twist-1 accounted for 80 and 71.5% of the reciprocal expression pattern in tissue arrays and clinicopathological tissue samples, respectively. This pattern was also detected in normal lung tissues, stage I and II lung cancer tissues, and adenocarcinoma subtypes of NSCLC tissues. Although cofilin-1 and Twist-1 were expressed inversely, a positive correlation of these two proteins was present in normal lung tissues and lung tumor tissues. Furthermore, enforced expression of cofilin-1 suppressed the expression level of Twist-1 in NSCLC H1299 cells. An on-line Kaplan-Meier survival analytic tool allowed access to a public microarray dataset with a maximum of 1,926 NSCLC samples. The analysis revealed that high expression levels of both cofilin-1 (CFL1) and Twist-1 (TWIST1) genes were associated with decreased survival of NSCLC patients, notably with regard to the adenocarcinoma subtype. The analysis was conducted using the multivariate Cox regression model. Although the reciprocal association of the expression levels of cofilin-1 and Twist-1 with the survival rate of NSCLC patients requires additional information, it may be a significant indicator of the progression of NSCLC.