The protein expression and clinical significance of metastasis-associated gene 1, matrix metalloproteinase-2 and coiled-coil domain containing 67 in papillary thyroid carcinoma

Abstract

Objective To investigate the expression of metastasis-associated gene 1 (MTA1), matrix metalloproteinase (MMP)-2 and coiled-coil domain containing 67 (CCDC67) proteins in papillary thyroid carcinoma (PTC) tissues and adjacent normal tissues so as to explore their clinical significance in the pathogenesis of PTC. Methods MTA1, MMP-2 and CCDC67 protein expression levels were detected by immunohistochemistry in 61 cases of PTC. A lentiviral expression vector carrying CCDC67 was constructed to obtain an efficient and stable expression of CCDC67 in TPC-1. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the MTA1, MMP-2 and CCDC67 mRNA levels in the cell line of PTC. Results The protein expression rate of CCDC67 in PTC tissue was lower than that in non-cancerous adjacent tissues (49.1% vs. 96.7%), and the expression rate of CCDC67 protein was related to tumor size, TNM stage, pathological grade and lymph node metastasis (χ2=3.911, 7.289, 10.353, 8.826, P=0.048, 0.007, 0.001, 0.003). The protein expression rate of MTA1 and MMP-2 in PTC tissues was higher than that in non-cancerous adjacent tissues (63.9% vs. 18.0%, 62.3% vs. 14.8%), and the expression rate of MTA1 and MMP-2 protein was related to PTC in TNM stage, pathological grade and lymph node metastasis (χ2=6.213, 12.752, 4.665, P=0.013, 0.000, 0.031; χ2=5.026, 5.026, 6.036, P=0.025, 0.025, 0.014). The expression levels of MTA1 and MMP-2 proteins both displayed a correlation to the expression of CCDC67 protein (χ2=7.634, r=0.334, P=0.006; χ2=6.139, r=0.302, P=0.013). There was obvious mRNA expression of MTA1 and MMP-2 in PTC cell line, and there was no detectable expression of CCDC67. The expression levels of MTA1 and MMP-2 mRNA in NC and CON groups were relatively down-regulated as compared with OE group. Conclusion The expression levels of MTA1, MMP-2 and CCDC67 were associated with the matastasis and invasion of PTC. As a tumor suppressor gene, CCDC67 may play an important role in the matastasis and invasion of PTC by inhibiting the expression of MTA1 and MMP-2. Key words: Papillary thyroid carcinoma; Metastasis-associated gene 1; Matrix metalloproteinase-2; Coiled-coil domain containing 67