Cyr61/CCN1 Overexpression Induces Epithelial-Mesenchymal Transition Leading to Laryngeal Tumor Invasion and Metastasis and Poor Prognosis

摘要

Background: To examine the expression of cysteine-rich 61 (Cyr61/CCN1) protein in laryngeal squamouscellcarcinoma (LSCC) tissues, and its relationship with the tumor epithelial-mesenchymal transition (EMT),invasion, metastasis, and prognosis. Materials and Methods: Immunohistochemistry was used to detect theexpressions of Cyr61, Vimentin (Vim), and E-cadherin (E-cad) in 88 cases of LSCC tissues and 30 cases oftumor-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 andhistopathological 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 ratewas significantly higher than that of the tumor-adjacent tissues, whereas E-cad expression rate was significantlylower than that of the tumor-adjacent tissues. The Vim expression rate was significantly higher in stages T3and T4 than in stages T1 and T2 LSCC tissues, whereas E-cad expression rate was significantly lower in stagesT3 and T4 than in stages T1 and T2 LSCC tissues. Compared to the group without lymph node metastasis, theVim expression rate was significantly higher and the E-cad expression rate was significantly lower in the groupwith lymph node metastasis. The expression rate of Cyr61 was significantly higher in LSCC tissues than in thetumor-adjacent normal tissues. In addition, the Cyr61 expression rate was higher in stages T3 and T4 than instages T1 and T2 LSCC, and higher in the group with lymph node metastasis than in the group without lymphnode metastasis. The Vim expression rate was significantly higher in the Cyr61 positive group than in the Cyr61negative group, whereas the E-cad expression rate was significantly higher in the Cyr61 negative group thanin the Cyr61 positive group. Survival analysis indicated that survival rates of Cyr61 positive, Vim positive andE-cad negative groups were significantly lower than that of Cyr61 negative, Vim negative and E-cad positivegroups, respectively. Conclusions: Cyr61 expression is closely associated with LSCC invasion and lymph nodemetastasis. Overexpression of Cyr61 may induce EMT and therefore leads to LSCC invasion and metastasisand poor prognosis. Cyr61 may become a new maker for clinical prediction of LSCC invasion and metastasisand a new target for LSCC treatment.