Pan-cancer Analysis and Single-cell Analysis Identifies the CENPN As a Biomarker for Survival Prognosis and Immunotherapy

Overview

Journal Discov Oncol

Publisher Springer

Date 2025 Jan 20

PMID 39832113

Authors

Nie Zhang

Zhuoying He

Xuejin Qin

Ke Han

Zhengchun Zhu

Fei Zhong

Affiliations

Soon will be listed here.

Abstract

Background: Centromere protein N (CENPN), located on chromosome 16q23.2, encodes vital nucleosome-associated complexes that are essential for dynamic assembly processes. CENPN plays a pivotal role in regulating cell proliferation and cell cycle progression by influencing mitotic events. Despite its potential importance, the precise functional role and regulatory mechanisms of CENPN in diverse malignancies remain largely unexplored. This study aimed to elucidate the role of CENPN in human cancers and evaluate its prognostic significance.

Methods: Investigate the role of CENPN in various malignancies, we leveraged data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. We employed a comprehensive suite of web platforms and software tools for data analysis, including R, Cytoscape, an integrated repository portal for tumor-immune system interactions (TISIDB), CBio Cancer Genomics Portal (cBioPortal), Search Tool for the Retrieval of Interaction Gene/Proteins (STRING), Gene Set Cancer Analysis (GSCALite), and a cancer single-cell state atlas (CancerSEA).

Results: The findings demonstrated that CENPN expression was elevated in the majority of cancer types and differentially expressed across molecular and immune subtypes. Functional enrichment analysis in multiple tumors also identified possible pathways of CENPN involvement in tumorigenesis. Its expression positively correlated with Th2 and Tcm cells in most cancers. It is also correlated with genetic markers of immunomodulators in various cancers.

Conclusions: Overall, CENPN expression is closely related to cancers and has the potential to act as a cancer biomarker.

References

Kumar P, Saini S, Prabhakar B . Cancer immunotherapy with check point inhibitor can cause autoimmune adverse events due to loss of Treg homeostasis. Semin Cancer Biol. 2019; 64:29-35. DOI: 10.1016/j.semcancer.2019.01.006. View

Hasan M, Malek M, Begum A, Rahman M, Haque Mollah M . Assessment of Drugs Toxicity and Associated Biomarker Genes Using Hierarchical Clustering. Medicina (Kaunas). 2019; 55(8). PMC: 6723056. DOI: 10.3390/medicina55080451. View

von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B . STRING: a database of predicted functional associations between proteins. Nucleic Acids Res. 2003; 31(1):258-61. PMC: 165481. DOI: 10.1093/nar/gkg034. View

Davis A, Grondin C, Johnson R, Sciaky D, Wiegers J, Wiegers T . Comparative Toxicogenomics Database (CTD): update 2021. Nucleic Acids Res. 2020; 49(D1):D1138-D1143. PMC: 7779006. DOI: 10.1093/nar/gkaa891. View

Oka N, Kasamatsu A, Endo-Sakamoto Y, Eizuka K, Wagai S, Koide-Ishida N . Centromere Protein N Participates in Cellular Proliferation of Human Oral Cancer by Cell-Cycle Enhancement. J Cancer. 2019; 10(16):3728-3734. PMC: 6636300. DOI: 10.7150/jca.32281. View

Chen F, Wendl M, Wyczalkowski M, Bailey M, Li Y, Ding L . Moving pan-cancer studies from basic research toward the clinic. Nat Cancer. 2022; 2(9):879-890. DOI: 10.1038/s43018-021-00250-4. View

Santucci C, Carioli G, Bertuccio P, Malvezzi M, Pastorino U, Boffetta P . Progress in cancer mortality, incidence, and survival: a global overview. Eur J Cancer Prev. 2020; 29(5):367-381. DOI: 10.1097/CEJ.0000000000000594. View

Chandrashekar D, Bashel B, Balasubramanya S, Creighton C, Ponce-Rodriguez I, Chakravarthi B . UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia. 2017; 19(8):649-658. PMC: 5516091. DOI: 10.1016/j.neo.2017.05.002. View

Diesendruck Y, Benhar I . Novel immune check point inhibiting antibodies in cancer therapy-Opportunities and challenges. Drug Resist Updat. 2017; 30:39-47. DOI: 10.1016/j.drup.2017.02.001. View

Palucka A, Coussens L . The Basis of Oncoimmunology. Cell. 2016; 164(6):1233-1247. PMC: 4788788. DOI: 10.1016/j.cell.2016.01.049. View

10.

Andres S, Bickett K, Alatoum M, Kalbfleisch T, Brock G, Wittliff J . Interaction between smoking history and gene expression levels impacts survival of breast cancer patients. Breast Cancer Res Treat. 2015; 152(3):545-56. DOI: 10.1007/s10549-015-3507-z. View

11.

Rahman M, Islam T, Gov E, Turanli B, Gulfidan G, Shahjaman M . Identification of Prognostic Biomarker Signatures and Candidate Drugs in Colorectal Cancer: Insights from Systems Biology Analysis. Medicina (Kaunas). 2019; 55(1). PMC: 6359148. DOI: 10.3390/medicina55010020. View

12.

Su F, Li W, Zhao X, Han Q, Xu X, Geng T . Risk Factors Analysis of Severe Liver Injury Induced by Statins. Horm Metab Res. 2023; 56(6):419-423. DOI: 10.1055/a-2210-3395. View

12.

Kennedy L, Salama A . A review of cancer immunotherapy toxicity. CA Cancer J Clin. 2020; 70(2):86-104. DOI: 10.3322/caac.21596. View

13.

Gui Z, Tian Y, Yu T, Liu S, Liu C, Zhang L . Clinical implications and immune features of CENPN in breast cancer. BMC Cancer. 2023; 23(1):851. PMC: 10496242. DOI: 10.1186/s12885-023-11376-2. View

14.

Bi G, Chen Z, Yang X, Liang J, Hu Z, Bian Y . Identification and validation of tumor environment phenotypes in lung adenocarcinoma by integrative genome-scale analysis. Cancer Immunol Immunother. 2020; 69(7):1293-1305. PMC: 11027644. DOI: 10.1007/s00262-020-02546-3. View

15.

Kops G, Weaver B, Cleveland D . On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer. 2005; 5(10):773-85. DOI: 10.1038/nrc1714. View

16.

Yuan H, Yan M, Zhang G, Liu W, Deng C, Liao G . CancerSEA: a cancer single-cell state atlas. Nucleic Acids Res. 2018; 47(D1):D900-D908. PMC: 6324047. DOI: 10.1093/nar/gky939. View

17.

Hoischen C, Yavas S, Wohland T, Diekmann S . CENP-C/H/I/K/M/T/W/N/L and hMis12 but not CENP-S/X participate in complex formation in the nucleoplasm of living human interphase cells outside centromeres. PLoS One. 2018; 13(3):e0192572. PMC: 5839545. DOI: 10.1371/journal.pone.0192572. View

18.

Mattei A, Bailly N, Meissner A . DNA methylation: a historical perspective. Trends Genet. 2022; 38(7):676-707. DOI: 10.1016/j.tig.2022.03.010. View