Expression of Gli-1 and EMT-related proteins and its clinical significance in non-small cell lung cancer / 中国肿瘤临床

ABSTRACT

Objective:To investigate the expression and clinical significance of glioma cancer-related gene homologous protein 1 (Gli-1) and epithelial-mesenchymal transition (EMT)-related proteins, namely, Snail, E-cadherin, and N-cadherin in non-small cell lung cancer (NSCLC). Methods:Immunohistochemical staining was performed to determine the expression levels of Gli-1, Snail, E-cadherin, and N-cadherin in 67 cases of NSCLC and 20 cases of normal lung tissues and its relationship with clinicopathological features and prognosis was explored. Another 20 samples of fresh NSCLC tissues and corresponding normal lung tissues were collected to detect the mRNA level through reverse transcription polymerase chain reaction (RT-PCR). Results:1) The positive rates of Gli-1, Snail, E-cadherin, and N-cadherin in NSCLC were 61.19％(41/67), 50.75％(34/67), 56.72％(38/67), and 53.73％(36/67), respectively;whereas those of normal lung tissues were 20％(4/20), 10％(2/20), 100％(20/20), and 5％(1/20), respectively. These two sets of data have significant statistical difference (P<0.05). 2) The high expression of Gli-1 in tumor tissues was closely related to lymph node metastasis, tumor, node, and metastasis (TNM) stage, and tumor differentiation (P<0.05) but was not associated with gender, age, tumor size, and pathological type. The expression of Gli-1 in NSCLC tissues was negatively correlated with E-cadherin (r=-0.325, P<0.05) and positively correlated with Snail and N-cadherin (r=0.379, r=0.490, P<0.05). 3) RT-PCR results showed that the expression levels of Gli-1, Snail, and N-cad-herin mRNA were significantly higher in NSCLC cases than in normal lung cases (P<0.05). The expression level of E-cadherin mRNA was lower in tumor tissues than in lung tissues (P<0.05). 4) Patients with high expression levels of Gli-1, Snail, and N-cadherin had signifi-cantly worse prognosis and lower survival rate than those with low expression (all P<0.05), whereas patients with low expression lev-els of E-cadherin had significantly better prognosis and lower survival rate than those with high expression (P<0.05). Multivariate Cox's proportional hazard regression analysis indicated that E-cadherin-negative group expression, lymph node metastasis, TNM stage, and tumor differentiation were independent prognostic factors for NSCLC. Conclusion: The abnormal activation of Hedgehog signaling pathway in NSCLC is correlated with EMT. Detecting the expression levels of Gli-1 and EMT-related proteins Snail, E-cadherin, and N-cadherin might be helpful in understanding the clinicopathological features and prognosis of patients with NSCLC.