Clinical significance of CCNE2 protein and mRNA expression in thyroid cancer tissues.

ABSTRACT

PURPOSE: Thyroid carcinoma (TC) is the most common endocrinal malignancy worldwide. Cyclin E2 (CCNE2), a member of the cyclin family, acts as a regulatory subunit of cyclin-dependent kinases (CDKs). It controls the transition of quiescent cells into the cell cycle, regulates the G1/S transition, promotes DNA replication, and activates CDK2. This study explored the role and potential molecular mechanisms of CCNE2 expression in TC tissues. MATERIAL/METHODS: Immunohistochemistry was used to evaluate the CCNE2 protein expression levels in TC. High-throughput data on CCNE2 in TC were obtained from RNA sequencing (RNA-seq), microarray, and literature data. The CCNE2 expression levels in TC were comprehensively assessed through an integrated analysis. Analyses of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPIs) data facilitated the investigation of the relative molecular mechanisms of CCNE2 in TC. RESULTS: The immunohistochemical experiment showed a significant increase in the expression of CCNE2 in the TC tissues. For 505 TC and 59 non-cancerous samples from RNA-seq data, the area under the curve (AUC) was 0.8016 (95% confidence interval [CI] 0.742-0.8612; p<0.001). With another 14 microarrays, the pool standard mean difference [SMD] was 1.01 (95% CI [0.82-1.19]). The pooled SMD of CCNE2 was 1.12 (95% CI [0.60-1.64]), and the AUC was 0.87 (95% CI [0.84-0.90]) for 1157 TC samples and 366 non-cancerous thyroid samples from all possible sources. Nine hub genes were upregulated in TC. CONCLUSIONS: A high expression of CCNE2 may lead to carcinogenesis and the development of TC.