文献检索，用中文搜 PubMed

BACKGROUND

ZBTB10 is a member of the zinc finger and bric-a-brac/tramtrack/broad (ZBTB) domain-containing protein family, reported to be associated with tumorigenesis and progression. However, its specific roles in oncogenesis, prognosis, and immune infiltration in stomach adenocarcinoma (STAD) remain to be elucidated.

METHODS

We analyzed ZBTB10 mRNA and protein expression profiling in STAD tissues using various bioinformatics tools, including TIMER2, GEO, Human Protein Atlas (HPA) databases, and R software. Survival analysis was performed through the Kaplan-Meier plotter. UALCAN and TCGA databases were used to evaluate the association of ZBTB10 expression with clinicopathological characteristics. Genetic alterations of ZBTB10 in human tumor samples were analyzed using the cBioPortal database. The correlation between ZBTB10 expression and immune cell infiltration was assessed using the TISIDB and CIBERSORT algorithms. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were applied to investigate the potential mechanism of ZBTB10 in STAD. Additionally, in vitro assays such as CCK-8, colony formation, and wound healing assays were performed to determine the biological role of ZBTB10 in STAD cells. Multiple immunohistochemistry (mIHC) was applied to characterize the association between immune cell infiltration and ZBTB10 expression in STAD tumor tissues.

RESULTS

Overall, ZBTB10 was differentially expressed in STAD compared to adjacent normal tissues, and higher ZBTB10 expression correlated with poorer overall survival (OS). Furthermore, GSEA and KEGG analysis suggested that ZBTB10 was predominantly involved in focal adhesion, PI3K-Akt signaling, and MAPK signaling pathways, suggesting its potential role in promoting tumor growth and progression. Moreover, based on the CIBERSORT algorithm, the expression of ZBTB10 was positively related to the levels of B cells, CD4 + T cells, M1 macrophages, and neutrophil cells. Meanwhile, ZBTB10 expression appeared to be negatively associated with tumor mutation burden (TMB) and microsatellite instability (MSI) in STAD, both of which influenced the efficacy of tumor immunotherapy. In vitro experiments demonstrated that ZBTB10 knockdown significantly inhibited tumor cell proliferation and invasion, and organoid area in STAD cell lines. The immune cell signature of CD45 was more prevalent with ZBTB10 expression in tumor tissue sections compared to adjacent normal tissues from STAD patients.

CONCLUSIONS

Upregulated ZBTB10 is significantly correlated with poor survival outcomes and immune infiltration in STAD, revealing that ZBTB10 may serve as a promising prognostic biomarker and a potential target for immunotherapy in STAD.

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

背景

ZBTB10 是含锌指和 bric-a-brac/tramtrack/broad（ZBTB）结构域蛋白家族的成员，据报道与肿瘤发生和进展相关。然而，其在胃腺癌（STAD）的肿瘤发生、预后及免疫浸润中的具体作用仍有待阐明。

方法

我们使用多种生物信息学工具，包括 TIMER2、GEO、人类蛋白质图谱（HPA）数据库和 R 软件，分析了 STAD 组织中 ZBTB10 的 mRNA 和蛋白质表达谱。通过 Kaplan-Meier 绘图仪进行生存分析。使用 UALCAN 和 TCGA 数据库评估 ZBTB10 表达与临床病理特征的关联。使用 cBioPortal 数据库分析人类肿瘤样本中 ZBTB10 的基因改变。使用 TISIDB 和 CIBERSORT 算法评估 ZBTB10 表达与免疫细胞浸润之间的相关性。应用基因集富集分析（GSEA）和京都基因与基因组百科全书（KEGG）通路来研究 ZBTB10 在 STAD 中的潜在机制。此外，进行了诸如 CCK-8、集落形成和伤口愈合试验等体外试验，以确定 ZBTB10 在 STAD 细胞中的生物学作用。应用多重免疫组织化学（mIHC）来表征 STAD 肿瘤组织中免疫细胞浸润与 ZBTB10 表达之间的关联。

结果

总体而言，与相邻正常组织相比，ZBTB10 在 STAD 中差异表达，ZBTB10 表达越高与总生存期（OS）越差相关。此外，GSEA 和 KEGG 分析表明，ZBTB10 主要参与粘着斑、PI3K-Akt 信号传导和 MAPK 信号传导通路，表明其在促进肿瘤生长和进展中的潜在作用。此外，基于 CIBERSORT 算法，ZBTB10 的表达与 B 细胞、CD4 + T 细胞、M1 巨噬细胞和中性粒细胞的水平呈正相关。同时，ZBTB10 表达在 STAD 中似乎与肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）呈负相关，这两者均影响肿瘤免疫治疗的疗效。体外实验表明，ZBTB10 敲低显著抑制了肿瘤细胞增殖和侵袭以及 STAD 细胞系中的类器官面积。与 STAD 患者的相邻正常组织相比，肿瘤组织切片中 CD45 的免疫细胞特征在 ZBTB10 表达时更为普遍。