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DEPDC1B:一种与结肠腺癌免疫浸润相关的新型肿瘤抑制基因。

DEPDC1B: A novel tumor suppressor gene associated with immune infiltration in colon adenocarcinoma.

作者信息

Zhu Dandan, Feng Huolun, Zhang Zhixiong, Li Jiaqi, Li Yong, Hou Tieying

机构信息

Guangdong Center for Clinical Laboratory, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.

School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.

出版信息

Cancer Med. 2024 Aug;13(15):e70043. doi: 10.1002/cam4.70043.

DOI:10.1002/cam4.70043
PMID:39087856
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11292854/
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

近期研究表明,含DEP结构域蛋白1B(DEPDC1B)与多种肿瘤的细胞周期呈正相关。然而,DEPDC1B在肿瘤免疫微环境(TIME)浸润中的作用仍未得到探索。

方法

我们使用R包“limma”和基因表达谱交互分析(GEPIA)网站分析了DEPDC1B在结肠腺癌(COAD)中的差异表达及预后意义。采用基因集富集分析(GSEA)研究DEPDC1B在COAD中表达的功能及相互作用。利用细胞计数试剂盒-8(CCK-8)实验和集落形成实验评估DEPDC1B的增殖功能。采用Spearman相关性分析和CIBERSORT检测DEPDC1B表达与肿瘤浸润免疫细胞、免疫检查点、肿瘤突变负荷(TMB)和微卫星不稳定性(MSI)状态之间的相关性。

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,预示着良好的预后。DEPDC1B mRNA在COAD细胞系中显著表达。CCK-8和集落形成实验表明,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与四种肿瘤浸润免疫细胞相关。此外,DEPDC1B高表达与PD-L1、CTLA4、SIGLEC15、PD-L2、TMB和MSI-H的表达相关。DEPDC1B高表达还表明对抗PD-L1免疫治疗有反应。

结论

DEPDC1B抑制COAD细胞的增殖并正向调节细胞周期,与CCNB1和PBK表达呈正相关。COAD中DEPDC1B的表达与肿瘤免疫微环境中的肿瘤浸润免疫细胞、免疫检查点、TMB和MSI-H相关。这表明DEPDC1B可能作为COAD的一种新型预后标志物和免疫治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/3386d642aad1/CAM4-13-e70043-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/f1ce36a935ac/CAM4-13-e70043-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/dd7dca4b5c84/CAM4-13-e70043-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/9e01fee8c5f4/CAM4-13-e70043-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/715eb82e2bb6/CAM4-13-e70043-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/051ea4ca8d7a/CAM4-13-e70043-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/3386d642aad1/CAM4-13-e70043-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/f1ce36a935ac/CAM4-13-e70043-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/dd7dca4b5c84/CAM4-13-e70043-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/155ecf2868cd/CAM4-13-e70043-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/481b45974808/CAM4-13-e70043-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/9e01fee8c5f4/CAM4-13-e70043-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/715eb82e2bb6/CAM4-13-e70043-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/051ea4ca8d7a/CAM4-13-e70043-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f08f/11292854/3386d642aad1/CAM4-13-e70043-g008.jpg

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本文引用的文献

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DEPDC1B promotes colorectal cancer via facilitating cell proliferation and migration while inhibiting apoptosis.DEP 结构域蛋白 1B 通过促进细胞增殖和迁移,同时抑制细胞凋亡,促进结直肠癌的发生。
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High Expression of DEPDC1B Predicts Poor Prognosis in Lung Adenocarcinoma.DEPDC1B的高表达预示肺腺癌预后不良。
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