RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
人类抗菌肽防御素β-1 在临床口腔鳞状细胞癌患者中的意义：一项整合生物信息学方法的研究
英文原题：Implications of Human Antimicrobial Peptide Defensin Beta-1 in Clinical Oral Squamous Cell Carcinoma Patients via an Integrated Bioinformatics Approach.
查看英文原题
Implications of Human Antimicrobial Peptide Defensin Beta-1 in Clinical Oral Squamous Cell Carcinoma Patients via an Integrated Bioinformatics Approach.
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研究概要
鉴于 DEFB1 在 OSCC 中的失调、预后价值以及与肿瘤进展相关的生物学通路改变，表明其具有肿瘤免疫调节作用，DEFB1 基因应被视为治疗口腔癌的潜在治疗靶点。
研究思路结论见上方概要
背景
人类抗菌肽防御素β1（DEFB1）已被发现在口腔疾病中发挥抗菌和抗炎作用；然而，其在口腔鳞状细胞癌（OSCC）中的肿瘤调控作用尚未通过整合生物信息学方法进行研究。
目的
探讨DEFB1基因在OSCC中的表达模式、预后价值、生物学功能及其对肿瘤免疫的意义，以研究其调控机制。
方法
通过TCGA数据库中的公开数据，研究了DEFB1基因在OSCC中的表达模式及调控参与。利用R软件工具和公共网络服务器对癌症及非癌样本的数据进行了统计分析。
结果
DEFB1在OSCC肿瘤样本中相较于健康对照口腔样本显著下调。DEFB1基因与OSCC的预后结果相关，其上调代表更好的生存结果。基因集富集分析（GSEA）结果显示，与DEFB1显著相关的基因主要富集于四条介导DEFB1在OSCC中抗肿瘤作用的信号通路，包括细胞外基质相关通路、RTK/PI3K/AKT/mTOR通路、角化作用以及细胞因子相关通路。基因-基因相互作用网络显示，DEFB1与若干基因密切相关，例如CCR6（C-C基序趋化因子受体6）、CXCL1（C-X-C基序趋化因子配体1）、MAP4K2（丝裂原活化蛋白激酶激酶激酶激酶2）、PTGER3（前列腺素E受体3）和MMP7（基质金属肽酶7）。此外，DEFB1被发现通过调节肿瘤巨噬细胞、肥大细胞、T细胞和NK细胞的功能参与OSCC的肿瘤免疫。
展开英文摘要原文
BACKGROUND
The human antimicrobial peptide defensin beta 1 (DEFB1) has been found to play antimicrobial and anti-inflammatory roles in oral diseases; however, its tumor-regulating role in oral squamous cell carcinoma (OSCC) has not yet been researched by using an integrative bioinformatics approach.
OBJECTIVE
To investigate the regulating mechanisms of the DEFB1 gene in OSCC in terms of its expression patterns, prognostic values, biological functions, and implication for tumor immunity.
METHODS
The DEFB1 gene expression pattern and regulatory involvement in OSCC were investigated using publically accessible data from TCGA database. R software tools and public web servers were utilized to conduct statistical analysis of data from cancer and noncancerous samples.
RESULTS
DEFB1 was found to be significantly downregulated in OSCC tumor samples compared with healthy control oral samples. The DEFB1 gene was found associated with the prognostic outcomes of OSCC, and its upregulation represented better survival outcome. Gene set enrichment analysis (GSEA) results showed that DEFB1-significantly correlated genes were mainly enriched in four signaling pathways mediating the antitumor role of DEFB1 in OSCC, including extracellular matrix-related pathway, RTK/PI3K/AKT/mTOR pathway, keratinization, and cytokine-related pathway. The gene-gene interaction network showed that DEFB1 was closely correlated with several genes, for example, CCR6 (C-C motif chemokine receptor 6), CXCL1 (C-X-C motif chemokine ligand 1), MAP4K2 (mitogen-activated protein kinase kinase kinase kinase 2), PTGER3 (prostaglandin E receptor 3), and MMP7 (matrix metallopeptidase 7). Moreover, DEFB1 was found to be involved in the tumor immunity of OSCC by regulating the function of tumor macrophage cells, mast cells, T cells, and NK cells.
CONCLUSIONS
Given the dysregulation, prognostic value, and tumor progression-related biological pathway alteration, indicating the tumor immune-modulatory role of DEFB1 in OSCC, the DEFB1 gene should be regarded as a potential therapeutic target for treating oral cancer.
论文信息
- 作者
- Li S、Li H、Xu Y、Ning W、Hu S、Wei S、Song H、Sun J
- 第一作者单位
- Stomatological Hospital, Southern Medical University, Guangzhou 510280, China.China
- 通讯作者单位
- Department of Stomatology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong Province 271000, China.China
- 文献类型
- 已撤稿
- 期刊
- Computational and mathematical methods in medicine2022
- 原文标识
- PubMed 35222682 · DOI 10.1155/2022/2203615
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