Yao Long, Liu Lianpo, Wu Jinsong, Huang Yunlong, Zhang Renquan, Zhang Haoxue
Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, 218# Ji Xi Road, Hefei, Anhui Province, China.
Department of Dermatovenerology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
Discov Oncol. 2025 Jul 11;16(1):1308. doi: 10.1007/s12672-025-02981-7.
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.
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.
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.
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.
据报道，兹维奇动粒蛋白（ZWILCH）可防止细胞过早退出有丝分裂。然而，ZWILCH在各种癌症的肿瘤免疫微环境中的潜在机制或作用在很大程度上仍不清楚。
在本研究中，通过全转录组分析观察到ZWILCH的普遍失调。利用空间转录组分析来确定ZWILCH的表达区域。接下来，使用单细胞转录组分析来确定肿瘤微环境中主要表达ZWILCH的细胞。此外，应用“CellChat”R包来评估ZWILCH对恶性细胞通讯的影响。结合多种分析方法，包括基因集富集分析（GSEA）、基因集变异分析（GSVA）、KEGG富集分析和Aucell，并利用TCPA功能蛋白数据、全基因组CRISPR筛选，深入探究了ZWILCH的潜在功能及其参与的信号通路。单因素Cox回归分析计算了ZWILCH与癌症患者不良预后之间的关联。
ZWILCH在肿瘤中普遍高表达。空间转录组分析表明，ZWILCH的过表达来自肿瘤区域或肿瘤混合区域。在单细胞水平上，ZWILCH主要由恶性细胞和增殖性T细胞表达。ZWILCH mRNA的表达与细胞增殖、DNA损伤修复和细胞周期评分呈正相关。ZWILCH高表达的患者中许多代谢途径受到抑制。此外，ZWILCH基因敲除后，大量癌细胞系停滞、受抑或死亡。此外，ZWILCH阳性表达的恶性细胞具有更强的细胞通讯能力。简而言之，ZWILCH是多种肿瘤临床预后的一个危险因素。
ZWILCH是一个有前景的治疗靶点，它通过参与细胞增殖、细胞通讯以及重塑不同癌症的肿瘤微环境来影响患者预后。
