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PLXDC1 可能是胃癌预后不良和免疫逃逸的生物标志物。

PLXDC1 Can Be a Biomarker for Poor Prognosis and Immune Evasion in Gastric Cancer.

作者信息

Li Xinwei, Fan Yongfei, Tang Mingyue, Li Huiyuan, Zhang Yue, Mi Jiaqi, Wang Yanyan, Zhao Menglin, Wang Zishu, Su Fang

机构信息

Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, People's Republic of China.

Department of Thoracic Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, 213003, People's Republic of China.

出版信息

J Inflamm Res. 2022 Sep 16;15:5439-5455. doi: 10.2147/JIR.S383191. eCollection 2022.

DOI:10.2147/JIR.S383191
PMID:36147688
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9488617/
Abstract

BACKGROUND

Research has revealed that Plexin domain containing 1 (PLXDC1) is correlated with the prognosis of a variety of tumors, but its role in the tumor microenvironment (TME) of gastric cancer has not been reported.

METHODS

In this study, we analyzed PLXDC1 expression in gastric cancer using the Oncomine and the Cancer Genome Atlas (TCGA) databases and immunohistochemical staining experiments, and performed prognostic assessment with data from the TCGA and Kaplan-Meier Plotter databases. The immunomodulatory role of PLXDC1 in the gastric cancer TME was analyzed by signaling pathway enrichment, immune cell correlation analysis, immunomodulator risk model construction and immunohistochemical staining experiments of immune cells.

RESULTS

The results indicated that PLXDC1 was overexpressed in gastric cancer and that its overexpression was associated with poor prognosis. Multivariate Cox analysis revealed that PLXDC1 could be an independent biomarker of the risk of gastric cancer. Signaling pathway enrichment revealed that high PLXDC1 expression was involved in signaling pathways related to immune activation and stromal activation, and Tumor Immune Dysfunction and Exclusion (TIDE) assessment indicated that high PLXDC1 expression was associated with a significantly higher risk of immune evasion than low PLXDC1 expression. A Cox risk model based on PLXDC1-associated immunomodulators also presented poor prognosis, and immune evasion was significantly higher in the high-risk group than in the low-risk group. In addition, immunohistochemical staining of CD8/CD3/CD4 T cells in the high and low PLXDC1 expression groups also observed immune cell distribution characteristics of immune evasion.

CONCLUSION

This study analyzed PLXDC1 from multiple biological perspectives and revealed that PLXDC1 can be a biomarker for poor prognosis and immune evasion in gastric cancer.

摘要

背景

研究表明，含Plexin结构域蛋白1（PLXDC1）与多种肿瘤的预后相关，但其在胃癌肿瘤微环境（TME）中的作用尚未见报道。

方法

在本研究中，我们使用Oncomine和癌症基因组图谱（TCGA）数据库以及免疫组织化学染色实验分析了PLXDC1在胃癌中的表达，并利用TCGA和Kaplan-Meier Plotter数据库的数据进行预后评估。通过信号通路富集、免疫细胞相关性分析、免疫调节因子风险模型构建以及免疫细胞的免疫组织化学染色实验，分析了PLXDC1在胃癌TME中的免疫调节作用。

结果

结果表明，PLXDC1在胃癌中过表达，其过表达与不良预后相关。多变量Cox分析显示，PLXDC1可能是胃癌风险的独立生物标志物。信号通路富集显示，高PLXDC1表达参与了与免疫激活和基质激活相关的信号通路，肿瘤免疫功能障碍与排除（TIDE）评估表明，高PLXDC1表达比低PLXDC1表达与更高的免疫逃逸风险显著相关。基于PLXDC1相关免疫调节因子的Cox风险模型也显示预后不良，高风险组的免疫逃逸明显高于低风险组。此外，高、低PLXDC1表达组中CD8/CD3/CD4 T细胞的免疫组织化学染色也观察到了免疫逃逸的免疫细胞分布特征。

结论

本研究从多个生物学角度分析了PLXDC1，揭示了PLXDC1可能是胃癌预后不良和免疫逃逸的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/cce77a0169ed/JIR-15-5439-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/9e7d0297a016/JIR-15-5439-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/c4107c828f0b/JIR-15-5439-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/875bd24e0e2d/JIR-15-5439-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/335012940458/JIR-15-5439-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/15b2e843c364/JIR-15-5439-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/e9763ac187dd/JIR-15-5439-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/a9413307edd9/JIR-15-5439-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/c0b2d75ad5e6/JIR-15-5439-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/cce77a0169ed/JIR-15-5439-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/9e7d0297a016/JIR-15-5439-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/c4107c828f0b/JIR-15-5439-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/875bd24e0e2d/JIR-15-5439-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/335012940458/JIR-15-5439-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/15b2e843c364/JIR-15-5439-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/e9763ac187dd/JIR-15-5439-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/a9413307edd9/JIR-15-5439-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/c0b2d75ad5e6/JIR-15-5439-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82f/9488617/cce77a0169ed/JIR-15-5439-g0009.jpg

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