Department of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China.
Department of Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
Aging (Albany NY). 2024 Jun 6;16(11):9784-9812. doi: 10.18632/aging.205899.
The zinc finger DHHC-type containing 1 (ZDHHC1) gene is implicated in the pathogenesis and progression of various malignant tumors, but its precise involvement in uterine corpus endometrial carcinoma (UCEC) remains unknown. Thus, this study investigated ZDHHC1 expression in UCEC using publicly available TCGA and Xena databases and elucidated the functions and mechanisms of the ZDHHC1 gene in UCEC progression using bioinformatics and experiments. The correlation between ZDHHC1 expression and prognosis, clinical features, immune cells, and RNA modifications of UCEC was evaluated using nomograms, correlation, ROC, and survival analyses. The impacts of ZDHHC1 overexpression on UCEC progression and mechanisms were explored with bioinformatics and experiments. Our study revealed that ZDHHC1 expression was significantly downregulated in UCEC and correlated with poor prognosis, cancer diagnosis, clinical stage, age, weight, body mass index, histological subtypes, residual tumor, tumor grade, and tumor invasion. Notably, Cox regression analysis and constructed nomograms showed that downregulated ZDHHC1 expression was a prognostic factor associated with poor prognosis in patients with UCEC. Conversely, above-normal ZDHHC1 expression inhibited the cell growth, cell cycle transition, migration, and invasion of UCEC cells, which may be related to the cell cycle, DNA replication, PI3K-AKT, and other pathways that promote tumor progression. Altered ZDHHC1 expression in UCEC was significantly associated with RNA modifications and the changes in cancer immune cell populations, such as CD56 bright NK cells, eosinophils, Th2 cells, and cell markers. In conclusion, considerably reduced ZDHHC1 expression in UCEC is associated with cancer cell growth, metastasis, poor prognosis, immune infiltration, and RNA modifications, revealing the promising potential of ZDHHC1 as a prognostic marker for UCEC.
锌指 DHHC 型含 1 型(ZDHHC1)基因与多种恶性肿瘤的发病机制和进展有关,但它在子宫体子宫内膜癌(UCEC)中的具体作用尚不清楚。因此,本研究使用公共 TCGA 和 Xena 数据库研究了 ZDHHC1 在 UCEC 中的表达,并通过生物信息学和实验阐明了 ZDHHC1 基因在 UCEC 进展中的功能和机制。使用列线图、相关性、ROC 和生存分析评估了 ZDHHC1 表达与 UCEC 预后、临床特征、免疫细胞和 RNA 修饰的相关性。通过生物信息学和实验探讨了 ZDHHC1 过表达对 UCEC 进展的影响及其机制。
我们的研究表明,ZDHHC1 在 UCEC 中的表达显著下调,与预后不良、癌症诊断、临床分期、年龄、体重、体重指数、组织学亚型、残留肿瘤、肿瘤分级和肿瘤侵袭相关。值得注意的是,Cox 回归分析和构建的列线图表明,下调的 ZDHHC1 表达是与 UCEC 患者预后不良相关的预后因素。相反,高于正常的 ZDHHC1 表达抑制了 UCEC 细胞的生长、细胞周期转变、迁移和侵袭,这可能与促进肿瘤进展的细胞周期、DNA 复制、PI3K-AKT 和其他途径有关。UCEC 中 ZDHHC1 表达的改变与 RNA 修饰和癌症免疫细胞群体的变化显著相关,如 CD56 阳性 NK 细胞、嗜酸性粒细胞、Th2 细胞和细胞标志物。
总之,UCEC 中 ZDHHC1 表达的显著降低与癌细胞的生长、转移、预后不良、免疫浸润和 RNA 修饰有关,这表明 ZDHHC1 作为 UCEC 预后标志物具有很大的潜力。