Expression and Significance of Cyclin-Dependent Protein Kinase 6 in Diffuse Large B-Cell Lymphoma

Abstract

Jing Li,1 Peng Li,2 Hong Su,1 Haonan Feng,3 Zhongyuan Bai,4 Yanfeng Xi1 1Department of Pathology, Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, Shanxi, 030013, People’s Republic of China; 2Department of Breast Surgery, Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, Shanxi, 030013, People’s Republic of China; 3Department of Pathology, Chengdu Second People’s Hospital, Chengdu, Sichuan, 610000, People’s Republic of China; 4Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of ChinaCorrespondence: Yanfeng Xi, Department of Pathology, Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, 3 Workers’ New Village Street, Xing Hua Ling, Taiyuan, Shanxi, 030013, People’s Republic of China, Email [email protected]: To study the relationship between cyclin-dependent protein kinase 6 (CDK6) expression in diffuse large B-cell lymphoma (DLBCL) and the clinical biological behavior and prognosis.Methods: Data mining was performed using the Oncomine and The Cancer Genome Atlas (TCGA) databases to analyze the expression level of CDK6 in DLBCL. CDK6 alterations in DLBCL and related functional networks were analyzed with c-BioPortal and the Gene Set Enrichment Analysis was performed by using DAVID and FunRich software. In addition, screening for differential gene expression of CDK6 was done and enriched by using LinkedOmics. Finally, formalin-fixed and paraffin-embedded (FFPE) tissue samples from 102 patients with DLBCL were collected from the Department of Pathology, Shanxi Cancer Hospital (Taiyuan, Shanxi, China) from January 2015 through December 2020. All cases had complete clinical course records. Thirty cases of lymph node reactive hyperplasia tissues were used as controls. The expression of CDK6 in DLBCL tissues was detected by qRT‑PCR and immunohistochemistry.Results: Bioinformatics analysis: The data showed that mRNA expression level and DNA copy number variations (CNVs) of CDK6 were significantly higher in DLBCL as compared to normal tissue (P ˂ 0.05). Based on C-BioPortal analysis, we speculated that amplification was the most common copy of CDK6 CNV in DLBCL. Through Gene Ontology (GO) analysis of these genes, it was found that the proteins were mainly located in the nucleus and cytoplasm. The biological interaction network of CDK6 alterations were found to participate primarily in the G1-S phase of the process. Analysis of LinkedOmics mRNA sequencing data showed that three genes were positively correlated with CDK6 expression: PSMD1, C2orf29 and ASB1. Through experimental verification, we found that CDK6 was overexpressed in DLBCL, and the expression of CDK6 mRNA and protein in DLBCL were positively correlated with Ann Arbor staging and IPI score (P< 0.05), and negatively correlated with overall survival (P< 0.001).Conclusion: Data mining results and experiments revealed and confirmed multi-level evidence for the importance of CDK6 in DLBCL; hence, CDK6 may be a potential marker in DLBCL. Thus, our study will perhaps lay the foundation for further research on the role of CDK6 in the genesis and development of DLBCL.Keywords: cyclin-dependent protein kinase 6, diffuse large B-cell lymphoma, bioinformatics analysis, prognosis

Keywords

• cyclin-dependent protein kinase 6
• diffuse large b-cell lymphoma
• bioinformatics analysis
• prognosis