The Clinical Significance and Potential Molecular Mechanism of Upregulated CDC28 Protein Kinase Regulatory Subunit 1B in Osteosarcoma

Chaohua Mo; Le Xie; Chang Chen; Jie Ma; Yingxin Huang; Yanxing Wu; Yuanyuan Xu; Huizhi Peng; Zengwei Chen; Rongjun Mao

doi:10.1155/2021/7228584

The Clinical Significance and Potential Molecular Mechanism of Upregulated CDC28 Protein Kinase Regulatory Subunit 1B in Osteosarcoma

J Oncol. 2021 Dec 10:2021:7228584. doi: 10.1155/2021/7228584. eCollection 2021.

Authors

Chaohua Mo¹, Le Xie¹, Chang Chen², Jie Ma³, Yingxin Huang¹, Yanxing Wu¹, Yuanyuan Xu¹, Huizhi Peng¹, Zengwei Chen¹, Rongjun Mao¹

Affiliations

¹ Department of Pathology, Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong 528300, China.
² Department of Pathology, Wuzhou Res Cross Hospital, Wuzhou, Guangxi Zhuang Autonomous Region 543100, China.
³ Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.

Abstract

Background: CDC28 Protein Kinase Regulatory Subunit 1B (CKS1B) is a member of cyclin-dependent kinase subfamily and the relationship between CKS1B and osteosarcoma (OS) remains to be explored.

Methods: 80 OS and 41 nontumor tissue samples were arranged to conduct immunohistochemistry (IHC) to evaluate CKS1B expression between OS and nontumor 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 CKS1B expression in OS. The effect of CKS1B expression on clinicopathological and overall survival of OS patients was measured through public high-throughput datasets, and analysis of immune infiltration and single-cell RNA-seq was applied to ascertain molecular mechanism of CKS1B in OS.

Results: A total of 197 OS samples and 83 nontumor 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 upregulation of CKS1B in OS (SMD = 1.38, 95% CI [0.52-2.25]) and the significant power of CKS1B expression in distinguishing OS samples from nontumor samples (Area under the Curve (AUC) = 0.89, 95% CI [0.86-0.91]). Clinicopathological and prognosis analysis indicated no remarkable significance but inference of immune infiltration and single-cell RNA-seq prompted that OS patients with overexpressed CKS1B were more likely to suffer OS metastasis while MYC Protooncogene may be the upstream regulon of CKS1B in proliferating osteoblastic OS cells.

Conclusions: In this study, sufficient evidence was provided for upregulation of CKS1B in OS. The advanced effect of CKS1B on OS progression indicates a foreground of CKS1B as a biomarker for OS.