Article Data

  • Views 472
  • Dowloads 135

Original Research

Open Access

Upregulation of the ZWINT expression correlates with prostate cancer progression and immune infiltration

  • Zonglin Li1
  • Xi Xiao1
  • Fuxiang Ye1
  • Yijun Cheng1
  • Jun Mi1,*,

1Department of Urology Surgery, The Second Hospital of Lanzhou University, 730030 Lanzhou, Gansu, China

DOI: 10.22514/jomh.2023.085 Vol.19,Issue 9,September 2023 pp.65-75

Submitted: 10 March 2023 Accepted: 06 April 2023

Published: 30 September 2023

*Corresponding Author(s): Jun Mi E-mail:


Prostate cancer (PCa), the most prevalent epithelial malignant neoplasm in the male group globally, is the fifth largest cause of cancer-related death in males. ZW10 Interactor (ZWINT) is involved in the chromosome segregation process, which is linked to the formation of several tumor cells. However, its function in PCa remains unknown. Therefore, our aim was to explore the potential mechanisms of ZWINT in PCa progression. We obtained RNA-seq as well as clinical data from The Cancer Genome Atlas Program (TCGA), University of California Santa Cruz (UCSC) database. Assessment of ZWINT expression in clinical subgroups, immune infiltration, and prognostic relevance using the R program. Search Tool for Recurring Instances of Neighbouring Genes (STRING) tool was applied to construct a ZWINT co-expression network and the potential biological functions involved in differentially expressed genes (DEGs) were investigated by enrichment analysis. ZWINT was upregulated in prostate cancer tissues and showed to be significantly associated with T stage, N stages, Gleason score (GS), and prognosis of prostate cancer patients. Functional enrichment analysis revealed that ZWINT-related genes were mainly related to cell cycle, meiosis, myogenic fiber synthesis, and muscle contraction. In addition, High-expression of ZWINT may have possessed immunosuppressive effects through adverse regulation of several immune cells and factors. ZWINT is overexpressed in prostate cancer and correlated with immune infiltration, which is expected to be a potential biomarker for PCa prognosis.


ZWINT; Prostate cancer; Bioinformatics; Immunity

Cite and Share

Zonglin Li,Xi Xiao,Fuxiang Ye,Yijun Cheng,Jun Mi. Upregulation of the ZWINT expression correlates with prostate cancer progression and immune infiltration. Journal of Men's Health. 2023. 19(9);65-75.


[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021; 71: 209–249.

[2] Sandhu S, Moore CM, Chiong E, Beltran H, Bristow RG, Williams SG. Prostate cancer. The Lancet. 2021; 398: 1075–1090.

[3] Wang G, Zhao D, Spring DJ, DePinho RA. Genetics and biology of prostate cancer. Genes & Development. 2018; 32: 1105–1140.

[4] Schröder FH, Hugosson J, Roobol MJ, Tammela TLJ, Zappa M, Nelen V, et al. Screening and prostate cancer mortality: results of the European randomised study of screening for prostate cancer (ERSPC) at 13 years of follow-up. The Lancet. 2014; 384: 2027–2035.

[5] Mahal BA, Yang DD, Wang NQ, Alshalalfa M, Davicioni E, Choeurng V, et al. Clinical and genomic characterization of low-prostate-specific antigen, high-grade prostate cancer. European Urology. 2018; 74: 146–154.

[6] Page EC, Bancroft EK, Brook MN, Assel M, Hassan Al Battat M, Thomas S, et al. Interim results from the IMPACT study: evidence for prostate-specific antigen screening in BRCA2 mutation carriers. European Urology. 2019; 76: 831–842.

[7] Aguiar JA, Li EV, Siddiqui MR, Soliman MA, Kumar SKSR, Schaeffer EM, et al. Utilization of genetic testing in men with advanced prostate cancer. The Prostate. 2023; 83: 516–523.

[8] Woo SD, Yeop YS, Chung WJ, Cho DH, Kim JS, Su OJ. Zwint-1 is required for spindle assembly checkpoint function and kinetochore-microtubule attachment during oocyte meiosis. Scientific Reports. 2015; 5: 15431.

[9] Vargas-Rondón N, Villegas VE, Rondón-Lagos M. The role of chromo-somal instability in cancer and therapeutic responses. Cancers. 2017; 10: 4.

[10] Famulski JK, Vos L, Sun X, Chan G. Stable hZW10 kinetochore residency, mediated by hZwint-1 interaction, is essential for the mitotic checkpoint. Journal of Cell Biology. 2008; 180: 507–520.

[11] Kops GJ, Kim Y, Weaver BA, Mao Y, McLeod I, Yates JR 3rd, et al. ZW10 links mitotic checkpoint signaling to the structural kinetochore. Journal of Cell Biology. 2005; 169: 49–60.

[12] Wang H, Hu X, Ding X, Dou Z, Yang Z, Shaw AW, et al. Human Zwint-1 specifies localization of zeste white 10 to kinetochores and is essential for mitotic checkpoint signaling. Journal of Biological Chemistry. 2004; 279: 54590–54598.

[13] Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M. A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Nature Cell Biology. 2004; 6: 1135–1141.

[14] Akabane S, Oue N, Sekino Y, Asai R, Thang PQ, Taniyama D, et al. KIFC1 regulates ZWINT to promote tumor progression and spheroid formation in colorectal cancer. Pathology International. 2021; 71: 441–452.

[15] Xu Z, Zhou Y, Cao Y, Dinh TLA, Wan J, Zhao M. Identification of candidate biomarkers and analysis of prognostic values in ovarian cancer by integrated bioinformatics analysis. Medical Oncology. 2016; 33: 130.

[16] Yang XY, Wu B, Ma SL, Yin L, Wu MC, Li AJ. Decreased expression of ZWINT is associated with poor prognosis in patients with HCC after surgery. Technology in Cancer Research & Treatment. 2018; 17: 1533033818794190.

[17] Peng F, Li Q, Niu S, Shen G, Luo Y, Chen M, et al. ZWINT is the next potential target for lung cancer therapy. Journal of Cancer Research and Clinical Oncology. 2019; 145: 661–673.

[18] Shao M, Hu Y, Ding H, Wu Q, Pan J, Zhao X, et al. The overexpression of ZWINT in integrated bioinformatics analysis forecasts poor prognosis in breast cancer. Translational Cancer Research. 2020; 9: 187–193.

[19] Zhou G, Shen M, Zhang Z. ZW10 binding factor (ZWINT), a direct target of mir-204, predicts poor survival and promotes proliferation in breast cancer. Medical Science Monitor. 2020; 26: e921659.

[20] Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology. 2014; 15: 550.

[21] Xia C, Dong X, Li H, Cao M, Sun D, He S, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chinese Medical Journal. 2022; 135: 584–590.

[22] Salagierski M, Schalken JA. Molecular diagnosis of prostate cancer: PCA3 and TMPRSS2:ERG gene fusion. The Journal of Urology. 2012; 187: 795–801.

[23] Ferro M, De Cobelli O, Lucarelli G, Porreca A, Busetto GM, Cantiello F, et al. Beyond PSA: the role of prostate health index (phi). International Journal of Molecular Sciences. 2020; 21: 1184.

[24] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144: 646–674.

[25] Guney Eskiler G, Deveci Ozkan A, Haciefendi A, Bilir C. Mechanisms of abemaciclib, a CDK4/6 inhibitor, induced apoptotic cell death in prostate cancer cells in vitro. Translational Oncology. 2022; 15: 101243.

[26] Ji J, Shen T, Li Y, Liu Y, Shang Z, Niu Y. CDCA5 promotes the progression of prostate cancer by affecting the ERK signalling pathway. Oncology Reports. 2021; 45: 921–932.

[27] Wan S, He Y, Zhang B, Yang Z, Du FM, Zhang CP, et al. Overexpression of CDCA8 predicts poor prognosis and promotes tumor cell growth in prostate cancer. Frontiers in Oncology. 2022; 12: 784183.

[28] Starr DA, Saffery R, Li Z, Simpson AE, Choo KH, Yen TJ, et al. HZwint-1, a novel human kinetochore component that interacts with HZW10. Journal of Cell Science. 2000; 113: 1939–1950.

[29] Yuan W, Xie S, Wang M, Pan S, Huang X, Xiong M, et al. Bioinformatic analysis of prognostic value of ZW10 interacting protein in lung cancer. OncoTargets and Therapy. 2018; 11: 1683–1695.

[30] Waltering KK, Helenius MA, Sahu B, Manni V, Linja MJ, Jänne OA, et al. Increased expression of androgen receptor sensitizes prostate cancer cells to low levels of androgens. Cancer Research. 2009; 69: 8141–8149.

[31] Urbanucci A, Sahu B, Seppälä J, Larjo A, Latonen LM, Waltering KK, et al. Overexpression of androgen receptor enhances the binding of the receptor to the chromatin in prostate cancer. Oncogene. 2012; 31: 2153–2163.

[32] Zhou H, Kuang J, Zhong L, Kuo W, Gray J, Sahin A, et al. Tumour ampli-fied kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nature Genetics. 1998; 20: 189–193.

[33] Lin Y, Chen Y, Wu G, Lee W. Hec1 sequentially recruits Zwint-1 and ZW10 to kinetochores for faithful chromosome segregation and spindle checkpoint control. Oncogene. 2006; 25: 6901–6914.

[34] Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nature Medicine. 2018; 24: 541–550.

[35] Greten FR, Grivennikov SI. Inflammation and cancer: triggers, mecha-nisms, and consequences. Immunity. 2019; 51: 27–41.

[36] Casey SC, Baylot V, Felsher DW. The MYC oncogene is a global regulator of the immune response. Blood. 2018; 131: 2007–2015.

[37] Ghatalia P, Gordetsky J, Kuo F, Dulaimi E, Cai KQ, Devarajan K, et al. Prognostic impact of immune gene expression signature and tumor infiltrating immune cells in localized clear cell renal cell carcinoma. Journal for ImmunoTherapy of Cancer. 2019; 7: 139.

[38] Want MY, Tsuji T, Singh PK, Thorne JL, Matsuzaki J, Karasik E, et al. WHSC1/NSD2 regulates immune infiltration in prostate cancer. Journal for ImmunoTherapy of Cancer. 2021; 9: e001374.

[39] Voskoboinik I, Smyth MJ, Trapani JA. Perforin-mediated target-cell death and immune homeostasis. Nature Reviews Immunology. 2006; 6: 940–952.

[40] Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nature Reviews Immunology. 2006; 6: 836–848.

[41] Ali S, Mann-Nüttel R, Schulze A, Richter L, Alferink J, Scheu S. Sources of type I interferons in infectious immunity: plasmacytoid dendritic cells not always in the driver’s seat. Frontiers in Immunology. 2019; 10: 778.

[42] Ho SS, Zhang WY, Tan NY, Khatoo M, Suter MA, Tripathi S, et al. The DNA structure-specific endonuclease MUS81 mediates DNA sensor STING-dependent host rejection of prostate cancer cells. Immunity. 2016; 44: 1177–1189.

[43] Bullock TNJ. CD40 stimulation as a molecular adjuvant for cancer vaccines and other immunotherapies. Cellular & Molecular Immunology. 2022; 19: 14–22.

[44] Yan C, Richmond A. Hiding in the dark: pan-cancer characterization of expression and clinical relevance of CD40 to immune checkpoint blockade therapy. Molecular Cancer. 2021; 20: 146.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Directory of Open Access Journals (DOAJ) DOAJ is a unique and extensive index of diverse open access journals from around the world, driven by a growing community, committed to ensuring quality content is freely available online for everyone.

SCImago The SCImago Journal & Country Rank is a publicly available portal that includes the journals and country scientific indicators developed from the information contained in the Scopus® database (Elsevier B.V.)

Publication Forum - JUFO (Federation of Finnish Learned Societies) Publication Forum is a classification of publication channels created by the Finnish scientific community to support the quality assessment of academic research.

Scopus: CiteScore 0.7 (2022) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Norwegian Register for Scientific Journals, Series and Publishers Search for publication channels (journals, series and publishers) in the Norwegian Register for Scientific Journals, Series and Publishers to see if they are considered as scientific. (

Submission Turnaround Time