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Prognostic implications of Kindlin proteins in human osteosarcoma

Authors Ning K, Zhang H, Wang Z, Li K

Received 22 October 2016

Accepted for publication 21 November 2016

Published 7 February 2017 Volume 2017:10 Pages 657—665

DOI https://doi.org/10.2147/OTT.S125418

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Dr Ingrid Espinoza

Kai Ning,* Haoshaqiang Zhang,* Zhigang Wang, Kun Li

Department of Orthopedics Surgery Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China

*These authors contributed equally to this work

Abstract: 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 P<0.01), but those of Kindlin-3 mRNA and protein were both dramatically lower (both P<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 P=0.01), presence of metastasis (both P=0.006), recurrence (both P=0.006) and poor response to chemotherapy (both P=0.02). Moreover, Kindlin-1 and Kindlin-2 expressions were both identified as independent prognostic factors for overall (both P=0.01) and disease-free (P=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.

Keywords: osteosarcoma, Kindlin protein family, clinicopathologic feature, overall survival, disease-free survival

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