Prognostic Implications of Kindlin Proteins in Human Osteosarcoma

The Kindlin protein family, comprising Kindlin-1, Kindlin-2 and Kindlin-3, play important roles in various human cancers. Here, to explore the clinical significance of Kindlins in human osteosarcomas, quantitative real-time PCR and Western blot analyses were performed to detect the expression of Kindlin-1, Kindlin-2 and Kindlin-3 mRNAs and proteins in 20 self-pairs of osteosarcoma and adjacent noncancerous tissues. Then, immunohistochemistry was performed to examine subcellular localizations and expression patterns of Kindlin proteins in 100 osteosarcoma and matched adjacent noncancerous tissues. Kindlin-1, Kindlin-2 and Kindlin-3 protein immunostainings were localized in the cytoplasm, nucleus and cytoplasm, respectively, of tumor cells in primary osteosarcoma tissues. Statistically, the expression levels of Kindlin-1 and Kindlin-2 mRNAs and proteins in osteosarcoma tissues were all significantly higher (both <0.01), but those of Kindlin-3 mRNA and protein were both dramatically lower (both <0.05), than in matched adjacent noncancerous tissues. In addition, the overexpressions of Kindlin-1 and Kindlin-2 proteins were both significantly associated with high tumor grade (both =0.01), presence of metastasis (both =0.006), recurrence (both =0.006) and poor response to chemotherapy (both =0.02). Moreover, Kindlin-1 and Kindlin-2 expressions were both identified as independent prognostic factors for overall (both =0.01) and disease-free (=0.02 and 0.01, respectively) survivals of osteosarcoma patients. However, no associations were observed between Kindlin-3 expression and various clinicopathologic features and patients' prognosis. In conclusion, aberrant expression of Kindlin-1 and Kindlin-2 may function as reliable markers for progression and prognosis in osteosarcoma patients, especially for tumor recurrence.