Cyr61/CCN1 overexpression induces epithelial-mesenchymal transition leading to laryngeal tumor invasion and metastasis and poor prognosis.

Background: To examine the expression of cysteine-rich 61 (Cyr61/CCN1) protein in laryngeal squamous- cell carcinoma (LSCC) tissues, and its relationship with the tumor epithelial-mesenchymal transition (EMT), invasion, metastasis, and prognosis.

Materials And Methods: Immunohistochemistry was used to detect the expressions of Cyr61, Vimentin (Vim), and E-cadherin (E-cad) in 88 cases of LSCC tissues and 30 cases of tumor-adjacent normal tissues. Vim and E-cad were used as mesenchymal and epithelial markers, respectively, to determine the relationship between Cyr61 expression and the EMT of LSCC cells. In addition, clinical and histopathological data were combined to analyze the relationship between the positive-expression rates of Cyr61, Vim and E-cad and LSCC invasion, metastasis and prognosis.

Results: In LSCC tissues, Vim expression rate was significantly higher than that of the tumor-adjacent tissues, whereas E-cad expression rate was significantly lower than that of the tumor-adjacent tissues. The Vim expression rate was significantly higher in stages T3 and T4 than in stages T1 and T2 LSCC tissues, whereas E-cad expression rate was significantly lower in stages T3 and T4 than in stages T1 and T2 LSCC tissues. Compared to the group without lymph node metastasis, the Vim expression rate was significantly higher and the E-cad expression rate was significantly lower in the group with lymph node metastasis. The expression rate of Cyr61 was significantly higher in LSCC tissues than in the tumor-adjacent normal tissues. In addition, the Cyr61 expression rate was higher in stages T3 and T4 than in stages T1 and T2 LSCC, and higher in the group with lymph node metastasis than in the group without lymph node metastasis. The Vim expression rate was significantly higher in the Cyr61 positive group than in the Cyr61 negative group, whereas the E-cad expression rate was significantly higher in the Cyr61 negative group than in the Cyr61 positive group. Survival analysis indicated that survival rates of Cyr61 positive, Vim positive and E-cad negative groups were significantly lower than that of Cyr61 negative, Vim negative and E-cad positive groups, respectively.

Conclusions: Cyr61 expression is closely associated with LSCC invasion and lymph node metastasis. Overexpression of Cyr61 may induce EMT and therefore leads to LSCC invasion and metastasis and poor prognosis. Cyr61 may become a new maker for clinical prediction of LSCC invasion and metastasis and a new target for LSCC treatment.