Integrated assessment of CDK1 upregulation in thyroid cancer

Am J Transl Res. 2019 Dec 15;11(12):7233-7254. eCollection 2019.

Abstract

Cyclin-dependent kinase 1 (CDK1) has a unique role in cell cycle regulation, as it is crucial for cell cycle progression and cell division. The aim of the present study was to use a combination of various detection methods to examine the expression and clinical significance of CDK1 in thyroid cancer (THCA). We used in-house tissue microarrays, immunohistochemistry, public RNA-sequencing, gene microarrays, and meta-analyses to conduct a comprehensive analysis of the role of CDK1 in the occurrence and development of THCA. CDK1 protein expression was notably higher in THCA tissues than in non-cancer tissues as evidenced by the in-house tissue microarrays. The expression of CDK1 protein was also significantly higher in pathologic T3-T4 than in T1-T2 samples. The pooled standardized mean difference (SMD) for CDK1 was 0.71 (95% CI, 0.46-0.95) including a total of 931 THCA and 585 non-cancerous thyroid tissue samples. An aggregation of the immunohistochemistry results and the RNA-sequencing/microarray findings gave a pooled SMD for CDK1 expression of 2.13 (95% CI, 1.30-2.96). The final area under curve (AUC) for the summarized receiver operating characteristic (sROC) was 0.7941 using all 1102 cases of THCA and 672 cases of controls. KEGG analysis with the co-expressed genes of CDK1 in THCA demonstrated the top enriched pathways to be the cell cycle, thyroid hormone synthesis, autoimmune thyroid disease, etc. In summary, we reveal the overexpression of CDK1 in THCA based on multiple detection methods that combine independent cohorts. However, further studies are required to elucidate the molecular mechanisms of CDK1 that promotes the biological aggressiveness of THCA cells.

Keywords: Cyclin-dependent kinase 1; RNA-sequencing; gene microarray; immunohistochemistry; thyroid cancer; tissue microarray.