Mitosis-related gene CENP-U as a potential biomarker in malignancy

Ann Transl Med. 2021 Dec;9(23):1744. doi: 10.21037/atm-21-6516.

Abstract

Background: Centromere protein U (CENP-U) is a component of the kinetochore and can regulate the cell cycle as a receptor of polo-like kinase 1 (PLK1). Recent studies have partially identified the role of CENP-U in tumor progression, but the underlying mechanisms of CENP-U in tumor immunity remain obscure.

Methods: We performed pan-cancer analysis to evaluate the role of CENP-U in immunity and proliferation with data from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE) datasets, and Genotype-Tissue Expression (GTEx) project. Results of CENP-U expression and related clinicopathological data were obtained to show the expression levels, prognosis, tumor progression, immune neoantigens, and immune checkpoints of CENP-U in 33 tumors. The Tumor Immune Estimation Resource (TIMER) dataset was used to analyze immune infiltration scores.

Results: Results of the pan-cancer analysis demonstrated that CENP-U is differentially expressed in normal tissues and common tumor tissues. Moreover, differentially expressed CENP-U was also identified between matched normal and tumor tissues, and the high expression level of CENP-U was associated with poor prognosis for 33 kinds of tumor except for that of thymoma (THYM) and lymphoid neoplasm diffuse large B-cell lymphoma (DLBC). Furthermore, the correlation between CENP-U expression and immune checkpoints and immune neoantigens was determined. In addition, CENP-U expression was correlated with tumor-infiltrating immune cells especially in THYM but not in lung squamous cell carcinoma (LUSC), esophageal carcinoma (ESCA), or lung adenocarcinoma (LUAD). Finally, gene set enrichment analysis (GSEA) indicated that CENP-U is critically involved in tumor proliferation, immunity, and metabolism.

Conclusions: CENP-U, a mitosis-related kinase, was found to be differentially expressed across different cancer types and to play an important role in tumor progression and immunity. CENP-U holds the potential to be a prognostic marker, whose targeting may provide therapeutic benefit.

Keywords: Centromere protein U (CENP-U); immunity; mitosis; pan-cancer analysis.