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Cited by 48Cancer Genomics and DiagnosticsCancer-related molecular mechanisms researchGenomics and Chromatin Dynamics

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Single-cell and bulk RNA sequencing analysis reveals CENPA as a potential biomarker and therapeutic target in cancers

Open access
Liu, Hengrui, Karsidag, Miray, Chhatwal, Kunwer, Wang, Panpan, Tang, Tao·2025·PLOS ONE
DOI 10.1371/journal.pone.0314745PMC PMC11737691

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Abstract

Background: Cancer remains one of the most significant public health challenges worldwide. A widely recognized hallmark of cancer is the ability to sustain proliferative signaling, which is closely tied to various cell cycle processes. Centromere Protein A (CENPA), a variant of the standard histone H3, is crucial for selective chromosome segregation during the cell cycle. Despite its importance, a comprehensive pan-cancer bioinformatic analysis of CENPA has not yet been conducted. Methods: Data on genomes, transcriptomes, and clinical information were retrieved from publicly accessible databases. We analyzed CENPA’s genetic alterations, mRNA expression, functional enrichment, association with stemness, mutations, expression across cell populations and cellular locations, link to the cell cycle, impact on survival, and its relationship with the immune microenvironment. Additionally, a prognostic model for glioma patients was developed to demonstrate CENPA’s potential as a biomarker. Furthermore, drugs targeting CENPA in cancer cells were identified and predicted using drug sensitivity correlations and protein-ligand docking. Results: CENPA exhibited low levels of gene mutation across various cancers. It was found to be overexpressed in nearly all cancer types analyzed in TCGA, relative to normal controls, and was predominantly located in the nucleus of malignant cells. CENPA showed a strong association with the cancer cell cycle, particularly as a biomarker for the G2 phase. It also emerged as a valuable diagnostic and prognostic biomarker across multiple cancer types. In glioma, CENPA demonstrated reliable prognostic potential when used alongside other prognostic factors. Additionally, CENPA was linked to the immune microenvironment. Drugs such as CD-437, 3-Cl-AHPC, Trametinib, BI-2536, and GSK461364 were predicted to target CENPA in cancer cells. Conclusion: CENPA serves as a crucial biomarker for the cell cycle in cancers, offering both diagnostic and prognostic value.

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Metadata

Authors
Liu, H., Karsidag, M., Chhatwal, K., Wang, P., & Tang, T.
Affiliations
  • Jinan University (CN)
  • First Affiliated Hospital of Jinan University (CN)
  • Sun Yat-sen University Cancer Center (CN)
Corresponding author
  • Wang, Panpan
  • Tang, Tao
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2025-01-16
Volume
20
Issue
1
Pages
e0314745
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0314745
PMC
PMC11737691
OpenAlex
W4406459740
Cited by
48
References
3
Citations by year
2026: 7 · 2025: 41
FWCI
21.63
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Preprints.org (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • K. C. Wong Education Foundation, the Natural Science Foundation of China (81603342)
  • Guangdong Basic and Applied Basic Research Foundation (2022A151501264, 2022A1515012641, 2024A1515012948)
  • Guangzhou Science and Technology Project (SL2023A03J00309, 2024A03J0154, 2023B01J1004)
  • Guangdong Provincial Bureau of Traditional Chinese Medicine Research Project (20221107)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
CENP-A, histone H3 variant, tumor markers, prognostic factors, therapeutic target, cell cycle, G2 phase, glioma, tumor immune microenvironment, drug response prediction, protein-ligand docking, pan-cancer analysis, single-cell RNA sequencing, bulk RNA-seq
MeSH terms
Centromere Protein A, Chromosomal Proteins, Non-Histone, Humans, Mutation, Neoplasms, Prognosis, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Sequence Analysis, RNA, Single-Cell Analysis, Tumor Microenvironment

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