关键词: biomarker cell cycle colon adenocarcinoma immunotherapy tumor‐infiltrating immune cells

Mesh : Humans Colonic Neoplasms / genetics immunology pathology metabolism Adenocarcinoma / genetics immunology pathology Tumor Microenvironment / immunology genetics Prognosis GTPase-Activating Proteins / genetics metabolism Cell Line, Tumor Gene Expression Regulation, Neoplastic Cell Proliferation Lymphocytes, Tumor-Infiltrating / immunology metabolism Epithelial-Mesenchymal Transition / genetics immunology Genes, Tumor Suppressor Biomarkers, Tumor / genetics metabolism Microsatellite Instability Male B7-H1 Antigen / genetics metabolism Cyclin B1 / genetics metabolism Female

来  源:   DOI:10.1002/cam4.70043   PDF(Pubmed)

Abstract:
BACKGROUND: Recent research indicates a positive correlation between DEP structural domain-containing 1B (DEPDC1B) and the cell cycle in various tumors. However, the role of DEPDC1B in the infiltration of the tumor immune microenvironment (TIME) remains unexplored.
METHODS: We analyzed the differential expression and prognostic significance of DEPDC1B in colon adenocarcinoma (COAD) using the R package \"limma\" and the Gene Expression Profiling Interactive Analysis (GEPIA) website. Gene set enrichment analysis (GSEA) was employed to investigate the functions and interactions of DEPDC1B expression in COAD. Cell Counting Kit-8 (CCK-8) assays and colony formation assays were utilized to assess the proliferative function of DEPDC1B. Correlations between DEPDC1B expression and tumor-infiltrating immune cells, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI) status were examined using Spearman correlation analysis and CIBERSORT.
RESULTS: DEPDC1B was highly expressed in COAD. Elevated DEPDC1B expression was associated with lower epithelial-to-mesenchymal transition (EMT) and TNM stages, leading to a favorable prognosis. DEPDC1B mRNA was prominently expressed in COAD cell lines. CCK-8 and colony formation assays demonstrated that DEPDC1B inhibited the proliferation of COAD cells. Analysis using the CIBERSORT database and Spearman correlation revealed that DEPDC1B correlated with four types of tumor-infiltrating immune cells. Furthermore, high DEPDC1B expression was linked to the expression of PD-L1, CTLA4, SIGLEC15, PD-L2, TMB, and MSI-H. High DEPDC1B expression also indicated responsiveness to anti-PD-L1 immunotherapy.
CONCLUSIONS: DEPDC1B inhibits the proliferation of COAD cells and positively regulates the cell cycle, showing a positive correlation with CCNB1 and PBK expression. DEPDC1B expression in COAD is associated with tumor-infiltrating immune cells, immune checkpoints, TMB, and MSI-H in the tumor immune microenvironment. This suggests that DEPDC1B may serve as a novel prognostic marker and a potential target for immunotherapy in COAD.
摘要:
背景:最近的研究表明,在各种肿瘤中,含DEP结构域的1B(DEPDC1B)与细胞周期之间呈正相关。然而,DEPDC1B在肿瘤免疫微环境(TIME)浸润中的作用尚待研究.
方法:我们使用R包“limma”和基因表达谱交互式分析(GEPIA)网站分析了DEPDC1B在结肠腺癌(COAD)中的差异表达和预后意义。采用基因集富集分析(GSEA)研究COAD中DEPDC1B表达的功能和相互作用。利用细胞计数试剂盒-8(CCK-8)测定和集落形成测定来评估DEPDC1B的增殖功能。DEPDC1B表达与肿瘤浸润免疫细胞的相关性,免疫检查点,肿瘤突变负荷(TMB),使用Spearman相关分析和CIBERSORT检查微卫星不稳定性(MSI)状态。
结果:DEPDC1B在COAD中高表达。DEPDC1B表达升高与较低的上皮-间质转化(EMT)和TNM分期相关,导致良好的预后。DEPDC1BmRNA在COAD细胞系中显著表达。CCK-8和集落形成试验证明DEPDC1B抑制COAD细胞的增殖。使用CIBERSORT数据库和Spearman相关性分析显示,DEPDC1B与四种类型的肿瘤浸润性免疫细胞相关。此外,高DEPDC1B表达与PD-L1、CTLA4、SIGLEC15、PD-L2、TMB、和MSI-H.高DEPDC1B表达还表明对抗PD-L1免疫疗法的反应性。
结论:DEPDC1B抑制COAD细胞的增殖,正向调节细胞周期,与CCNB1和PBK表达呈正相关。DEPDC1B在COAD中的表达与肿瘤浸润免疫细胞有关,免疫检查点,TMB,和肿瘤免疫微环境中的MSI-H。这表明DEPDC1B可能作为一种新的预后标志物和COAD免疫治疗的潜在靶标。
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