Cyclin-dependent kinase 12 (CDK12) in chordoma: prognostic and therapeutic value.

European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society
Pichaya ThanindratarnZhenfeng Duan

Abstract

To determine the cyclin-dependent kinase 12 (CDK12) expression in chordoma patient tissues and cell lines, its correlation with oncologic outcomes, and its function in chordoma cell proliferation. A chordoma tissue microarray was constructed from fifty-six patient specimens and examined by immunohistochemistry to measure CDK12 expression and its correlation to patient clinical characteristics and survival. CDK12 expression in chordoma cell lines and patient tissues was evaluated via western blot. CDK12 specific small interfering RNA (siRNA) was applied to determine whether its inhibition attenuated chordoma cell growth and proliferation. CDK12 was expressed in the majority of chordoma specimens, with notably higher expression in patients with recurrent or metastatic disease. High CDK12 expression was an independent prognostic predictor for shorter overall and progression-free survival in chordoma by univariate and multivariate analysis. Western blot analysis revealed that CDK12 was also highly expressed in chordoma cell lines, with CDK12 specific small interfering RNA (siRNA) mediated knockdown decreasing proliferation and inducing apoptosis. Mechanistically, inhibition of CDK12 decreased phosphorylation of RNA polymerase II (R...Continue Reading

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Sep 17, 2021·World Neurosurgery·Cas VanderheijdenKoos Hovinga

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