Zwilch kinetochore protein affects the prognosis of cancer patients by participating in cell proliferation, enhancing cell communication, and reshaping the tumor microenvironment.

Background: Zwilch Kinetochore Protein(ZWILCH) has been reported to prevent cells from prematurely exiting mitosis. However, the underlying mechanisms or involvement of ZWILCH in the tumor immune microenvironment in various cancers remain largely unknown.

Methods: Generalized dysregulation of ZWILCH was observed through the whole transcriptome analysis in this study. The spatial transcriptome analysis was utilized to identify expressed regions of ZWILCH. Next, cells that mainly expressed ZWILCH in the tumor microenvironment were determined using the single-cell transcriptome analysis. Also, the "cellchat" R package was applied to estimate the effect of ZWILCH on malignant cell communication. Combining multiple analytic approaches including GSEA, GSVA, KEGG enrichment analysis, and Aucell, with TCPA functional protein data, Genome-wide CRISPR screening, potential functions of ZWILCH and the pathways in which ZWILCH participated were thoroughly exploited. Univariate Cox regression analysis calculated the association between ZWILCH and cancer patients' adverse outcomes.

Results: ZWILCH is universally highly expressed in tumors. The spatial transcriptome analysis showed that ZWILCH overexpression comes from the tumoral region or mixed tumoral region. At the single-cell level, ZWILCH is chiefly expressed by malignant cells and proliferative T cells. The expression of ZWILCH mRNA is positively correlated with cell proliferation, repair of DNA damage, and cell cycle score. Plenty of metabolic pathways are inhibited in patients with high expression of ZWILCH. Moreover, after ZWILCH knockout, a large number of cancer cell lines are stagnated, inhibited, or died. Additionally, the malignant cells with positive expression of ZWILCH have a stronger ability for cell communication. In short, ZWILCH is meant to be a risk factor for clinical outcomes of multiple tumors.

Conclusions: ZWILCH is a promising therapeutic target that influences patient prognosis by participating in cell proliferation, cell communication, and reshaping the tumor microenvironment across different cancers.