Increased expression of kindlin-2 is correlated with hematogenous metastasis and poor prognosis in patients with clear cell renal cell carcinoma

Kindlin-2 is involved in activating the integrin signaling pathway which plays an important role in regulating cancer cell invasion. However, the role of kindlin-2 may vary among cancer types. The aim of this study was to explore the possible association between kindlin-2 and clear cell renal cell carcinoma (ccRCC), and its potential role in the prognosis of ccRCC. Immunohistochemistry assays were used to examine kindlin-2 expression levels in cancer tissues obtained from 336 patients with ccRCC. The correlation between kindlin-2 expression levels and pathologic variables was then analyzed. In addition, the association between kindlin-2 expression levels and survival time was analyzed by Kaplan-Meier survival curves and log-rank tests. Of 336 ccRCC patients, 199 had high levels of kindlin-2 expression, while 137 had low kindlin-2 expression levels. Patients at a late stage of ccRCC (stage III or IV) were more likely to have high kindlin-2 expression levels than those at an early stage (stage I or II) (chi(2) = 4.72, P = 0.03). Patients with high levels of kindlin-2 expression had higher risk of hematogenous metastasis (chi(2) = 6.70, P = 0.01) than those with low levels of kindlin-2 expression. In addition, the survival time was significantly shorter for patients with high levels of kindlin-2 expression than for those with low levels of kindlin-2 expression (P = 0.001 for overall survival [OS] and P = 0.002 for disease-free survival [DFS]). Multivariate survival analysis based on the Cox proportional hazards model showed that high kindlin-2 expression levels had a hazard risk (HR) of 1.76 for OS (95% CI 1.19-2.62, P = 0.005) and an HR of 1.47 for DFS (95% CI = 1.05-2.06, P = 0.026). By comparison, lymph node metastasis had an HR of 1.48 for OS (95% CI 1.04-2.10, P = 0.029) and an HR of 1.41 for DFS (95% CI 1.04-1.93, P = 0.029). This study provided strong evidence that increased kindlin-2 expression might be involved in promoting tumor invasiveness and leading to a poor prognosis of ccRCC.