Clinicopathological value of the upregulation of cyclin-dependent kinases regulatory subunit 2 in osteosarcoma.

ABSTRACT

BACKGROUND: Cyclin-dependent kinase subunit 2 (CKS2) is a member of cyclin dependent kinase subfamily and the relationship between CKS2 and osteosarcoma (OS) remains to be further analyzed. METHODS: 80 OS and 41 non-tumor tissue samples were arranged to perform immunohistochemistry (IHC) to evaluate CKS2 expression between OS and non-tumor samples. The standard mean deviation (SMD) was calculated based on in-house IHC and tissue microarrays, and exterior high-throughput datasets for further verification of CKS2 expression trend in OS. The effect of CKS2 expression on clinicopathological parameters of OS patients, and single-cell in OS tissues was analyzed through public high-throughput datasets and functional enrichment analysis was conducted for co-expression genes of CKS2 in accordance with weighted correlation network analysis. RESULTS: A total of 217 OS samples and 87 non-tumor samples (including tissue and cell line) were obtained from in-house IHC, microarrays and exterior high-throughput datasets. The analysis of integrated expression status demonstrated up-regulation of CKS2 in OS (SMD = 1.57, 95%CI [0.27-2.86]) and the significant power of CKS2 expression in distinguishing OS samples from non-tumor samples (AUC = 0.97 95%CI [0.95-0.98]). Clinicopathological analysis of GSE21257 indicated that OS patients with higher CKS2 expression was more likely to suffer OS metastasis. Although Kaplan-Meier curves showed no remarkable difference of overall survival rate between OS patients with high and low-CKS2, CKS2 was found up-regulated in proliferating osteosarcoma cells. Co-expression genes of CKS2 were mainly assembled in function and pathways such as cell cycle, cell adhesion, and intercellular material transport. CONCLUSIONS: In summary, up-regulation of CKS2 expression in OS tissue was found through multiple technical approaches. In addition, scRNA-seq and co-expression analysis showed that CKS2 may have an impact on important biological process linked with cell cycle, cell adhesion, and intercellular material transport. Present study on CKS2 in OS indicated a promising prospect for CKS2 as a biomarker for OS.