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) (χ(2) = 4.72, P = 0.03). Patients with high levels of kindlin‐2 expression had higher risk of hematogenous metastasis (χ(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.