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Open Access 01-12-2023 | Research

Prognostic and immune infiltrative biomarkers of CENPO in pan–cancer and its relationship with lung adenocarcinoma cell proliferation and metastasis

Authors: Yuanbiao Wang, Daowen Ye, Ying Li, Fenghong Lv, Wanbo Shen, Hui Li, Linghan Tian, Zongling Fan, Yanling Li, Yan wang, Feng Li, Yan Chen

Published in: BMC Cancer | Issue 1/2023

Abstract

Background

The centromere protein O (CENPO) is an important member of the centromere protein family. However, the role of CENPO in pan–cancer and immune infiltration has not been reported. Here, we investigated the role of CENPO in pan–cancer and further validated its role in lung adenocarcinoma (LUAD) by in vitro experiments.

Method

The UCSC Xena database and The Cancer Genome Atlas (TCGA)–LUAD data were used to assess the expression levels of CENPO. The potential value of CENPO as a diagnostic and prognostic biomarker for pan–cancer was evaluated using TCGA data and the GEPIA database. The -expression profiles of LUAD patients and the corresponding clinical data were downloaded for correlation analysis. The role of CENPO in immune infiltration was investigated using the UCSC Xena database. Subsequently, qRT–PCR was performed to detect the expression of CENPO. Cell proliferation, migration, and invasion were determined using CCK–8, wound–healing assay, and transwell assay, respectively.

Results

CENPO is highly expressed in most cancers, and the upregulation of CENPO is associated with poor prognosis in many cancers. CENPO expression correlates with age, TNM stage, N stage, T stage, and receipt of radiotherapy in LUAD patients, and LUAD patients with high CENPO expression have poorer overall survival (OS) and disease–free survival (DFS). In addition, CENPO expression is associated with immune cell infiltration and immune checkpoint inhibitors. Moreover, the expression of CENPO was closely related to the expression of tumor mutational load and microsatellite instability. In vitro experiments showed that CENPO expression was increased in LUAD cell lines and that knockdown of CENPO significantly inhibited the proliferation, cell invasion, and migration ability of LUAD cells.

Conclusion

CENPO may be a potential pan–cancer biomarker and oncogene, especially in LUAD. In addition, CENPO is associated with immune cell infiltration and may serve as a new molecular therapeutic target and effective prognostic marker for LUAD.

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Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49.CrossRefPubMed

Dyba T, Randi G, Bray F, Martos C, Giusti F, Nicholson N, Gavin A, Flego M, Neamtiu L, Dimitrova N, et al. The European cancer burden in 2020: Incidence and mortality estimates for 40 countries and 25 major cancers. Eur J Cancer. 2021;157:308–47.CrossRefPubMedPubMedCentral

Durante M, Reppingen N, Held K. Immunologically augmented cancer treatment using modern radiotherapy. Trends Mol Med. 2013;19(9):565–82.CrossRefPubMed

Hashim D, Boffetta P, La Vecchia C, Rota M, Bertuccio P, Malvezzi M, Negri E. The global decrease in cancer mortality: trends and disparities. Ann Oncol. 2016;27(5):926–33.CrossRefPubMed

Li W, Liu J. The Prognostic and Immunotherapeutic Significance of AHSA1 in Pan-Cancer, and Its Relationship With the Proliferation and Metastasis of Hepatocellular Carcinoma. Front Immunol. 2022;13:845585.CrossRefPubMedPubMedCentral

Feng Z, Chen Y, Cai C, Tan J, Liu P, Chen Y, Shen H, Zeng S, Han Y. Pan-Cancer and Single-Cell Analysis Reveals CENPL as a Cancer Prognosis and Immune Infiltration-Related Biomarker. Front Immunol. 2022;13:916594.CrossRefPubMedPubMedCentral

Pan-cancer analysis of whole genomes. Nature. 2020;578(7793):82–93.CrossRef

Weinstein J, Collisson E, Mills G, Shaw K, Ozenberger B, Ellrott K, Shmulevich I, Sander C, Stuart J. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet. 2013;45(10):1113–20.CrossRefPubMedPubMedCentral

Sharma A, Dimitrov S, Hamiche A, Van Dyck E. Centromeric and ectopic assembly of CENP-A chromatin in health and cancer: old marks and new tracks. Nucleic Acids Res. 2019;47(3):1051–69.CrossRefPubMed

10.

Ding N, Li R, Shi W, He C. CENPI is overexpressed in colorectal cancer and regulates cell migration and invasion. Gene. 2018;674:80–6.CrossRefPubMed

11.

Liu Y, Yao Y, Liao B, Zhang H, Yang Z, Xia P, Jiang X, Ma W, Wu X, Mei C, et al. A positive feedback loop of CENPU/E2F6/E2F1 facilitates proliferation and metastasis via ubiquitination of E2F6 in hepatocellular carcinoma. Int J Biol Sci. 2022;18(10):4071–87.CrossRefPubMedPubMedCentral

12.

Cao Y, Xiong J, Li Z, Zhang G, Tu Y, Wang L, Jie Z. CENPO expression regulates gastric cancer cell proliferation and is associated with poor patient prognosis. Mol Med Rep. 2019;20(4):3661–70.PubMedPubMedCentral

13.

Hori T, Okada M, Maenaka K, Fukagawa T. CENP-O class proteins form a stable complex and are required for proper kinetochore function. Mol Biol Cell. 2008;19(3):843–54.CrossRefPubMedPubMedCentral

14.

Zhang S, Xie Y, Tian T, Yang Q, Zhou Y, Qiu J, Xu L, Wen N, Lv Q, Du Z. High expression levels of centromere protein A plus upregulation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling pathway affect chemotherapy response and prognosis in patients with breast cancer. Oncol Lett. 2021;21(5):410.CrossRefPubMedPubMedCentral

15.

Liu Z, Chen C, Yan M, Zeng X, Zhang Y, Lai D. CENPO regulated proliferation and apoptosis of colorectal cancer in a p53-dependent manner. Discov Oncol. 2022;13(1):8.CrossRefPubMedPubMedCentral

16.

Liu Y, Xiong S, Liu S, Chen J, Yang H, Liu G, Li G. Analysis of Gene Expression in Bladder Cancer: Possible Involvement of Mitosis and Complement and Coagulation Cascades Signaling Pathway. J Comput Biol. 2020;27(6):987–98.CrossRefPubMed

17.

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W, Smyth G. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.CrossRefPubMedPubMedCentral

18.

Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, Feng T, Zhou L, Tang W, Zhan L, et al. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation (Camb). 2021;2(3):100141.PubMed

19.

Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28(1):27–30.CrossRefPubMedPubMedCentral

20.

Park C, Jeong K, Park J, Jung S, Bae J, Kim K, Ock C, Kim M, Keam B, Kim T, et al. Pan-cancer methylation analysis reveals an inverse correlation of tumor immunogenicity with methylation aberrancy. Cancer Immunol Immunother. 2021;70(6):1605–17.CrossRefPubMed

21.

Ba-Alawi W, Nair S, Li B, Mammoliti A, Smirnov P, Mer A, Penn L, Haibe-Kains B. Bimodal Gene Expression in Patients with Cancer Provides Interpretable Biomarkers for Drug Sensitivity. Can Res. 2022;82(13):2378–87.CrossRef

22.

Liu X, Wang H, Zhao G. Centromere Protein A Goes Far Beyond the Centromere in Cancers. Mol Cancer Res. 2022;20(1):3–10.CrossRefPubMed

23.

Slee R, Steiner C, Herbert B, Vance G, Hickey R, Schwarz T, Christan S, Radovich M, Schneider B, Schindelhauer D, et al. Cancer-associated alteration of pericentromeric heterochromatin may contribute to chromosome instability. Oncogene. 2012;31(27):3244–53.CrossRefPubMed

24.

Berglund A, Mills M, Putney R, Hamaidi I, Mulé J, Kim S. Methylation of immune synapse genes modulates tumor immunogenicity. J Clin Investig. 2020;130(2):974–80.CrossRefPubMedPubMedCentral

25.

Chen C, Yin N, Yin B, Lu Q. DNA methylation in thoracic neoplasms. Cancer Lett. 2011;301(1):7–16.CrossRefPubMed

26.

Samel A, Cuomo A, Bonaldi T, Ehrenhofer-Murray A. Methylation of CenH3 arginine 37 regulates kinetochore integrity and chromosome segregation. Proc Natl Acad Sci USA. 2012;109(23):9029–34.CrossRefPubMedPubMedCentral

27.

Anderson N, Simon M. The tumor microenvironment. Current biology : CB. 2020;30(16):R921–5.CrossRefPubMed

28.

Zhang S, Zhang E, Long J, Hu Z, Peng J, Liu L, Tang F, Li L, Ouyang Y, Zeng Z. Immune infiltration in renal cell carcinoma. Cancer Sci. 2019;110(5):1564–72.CrossRefPubMedPubMedCentral

29.

Wu Z, Chen H, Luo W, Zhang H, Li G, Zeng F, Deng F. The Landscape of Immune Cells Infiltrating in Prostate Cancer. Front Oncol. 2020;10:517637.CrossRefPubMedPubMedCentral

30.

Xu C, Sui S, Shang Y, Yu Z, Han J, Zhang G, Ntim M, Hu M, Gong P, Chen H, et al. The landscape of immune cell infiltration and its clinical implications of pancreatic ductal adenocarcinoma. J Adv Res. 2020;24:139–48.CrossRefPubMedPubMedCentral

31.

Brassart-Pasco S, Brézillon S, Brassart B, Ramont L, Oudart J, Monboisse J. Tumor Microenvironment: Extracellular Matrix Alterations Influence Tumor Progression. Front Oncol. 2020;10:397.CrossRefPubMedPubMedCentral

32.

Borst J, Ahrends T, Bąbała N, Melief C, Kastenmüller W. CD4 T cell help in cancer immunology and immunotherapy. Nat Rev Immunol. 2018;18(10):635–47.CrossRefPubMed

33.

Raskov H, Orhan A, Christensen J, Gögenur I. Cytotoxic CD8 T cells in cancer and cancer immunotherapy. Br J Cancer. 2021;124(2):359–67.CrossRefPubMed

34.

Bi J, Tian Z. NK Cell Dysfunction and Checkpoint Immunotherapy. Front Immunol. 1999;2019:10.

35.

Tan Y, Wang M, Zhang Y, Ge S, Zhong F, Xia G, Sun C. Tumor-Associated Macrophages: A Potential Target for Cancer Therapy. Front Oncol. 2021;11:693517.CrossRefPubMedPubMedCentral

36.

Schmieder A, Michel J, Schönhaar K, Goerdt S, Schledzewski K. Differentiation and gene expression profile of tumor-associated macrophages. Semin Cancer Biol. 2012;22(4):289–97.CrossRefPubMed

37.

Zhang J, Yuan X, Wang Y, Liu J, Li Z, Li S, Liu Y, Gong X, Sun Y, Wu W, et al. Tumor-Associated Macrophages Correlate With Prognosis in Medulloblastoma. Front Oncol. 2022;12:893132.CrossRefPubMedPubMedCentral

38.

Xu H, Xu Q, Yin L. Prognostic value of tumor immune cell infiltration patterns in colon adenocarcinoma based on systematic bioinformatics analysis. Cancer Cell Int. 2021;21(1):344.CrossRefPubMedPubMedCentral

39.

Bruni D, Angell H, Galon J. The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy. Nat Rev Cancer. 2020;20(11):662–80.CrossRefPubMed

40.

Mlecnik B, Bindea G, Angell H, Maby P, Angelova M, Tougeron D, Church S, Lafontaine L, Fischer M, Fredriksen T, et al. Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability. Immunity. 2016;44(3):698–711.CrossRefPubMed

41.

Toor S, Sasidharan Nair V, Decock J, Elkord E. Immune checkpoints in the tumor microenvironment. Semin Cancer Biol. 2020;65:1–12.CrossRefPubMed

42.

Kocikowski M, Dziubek K, Parys M: Hyperprogression Under Immune Checkpoint-Based Immunotherapy-Current Understanding, The Role of PD-1/PD-L1 Tumour-Intrinsic Signalling, Future Directions and a Potential Large Animal Model. Cancers 2020, 12(4).

43.

Shao C, Wang Y, Duan H, Ding P, Zhang Y, Ning J, Han J, Jiang T, Yan X. CENP-UMitosis-related gene as a potential biomarker in malignancy. Ann Transl Med. 2021;9(23):1744.CrossRefPubMedPubMedCentral

Title: Prognostic and immune infiltrative biomarkers of CENPO in pan–cancer and its relationship with lung adenocarcinoma cell proliferation and metastasis
Authors: Yuanbiao Wang
Daowen Ye
Ying Li
Fenghong Lv
Wanbo Shen
Hui Li
Linghan Tian
Zongling Fan
Yanling Li
Yan wang
Feng Li
Yan Chen
Publication date: 01-12-2023
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-023-11233-2

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