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ADAM9 免疫学功能与预后价值的泛癌研究,尤其在肝癌中

英文原题:A pan-cancer study of ADAM9's immunological function and prognostic value particularly in liver cancer.

查看英文原题

A pan-cancer study of ADAM9's immunological function and prognostic value particularly in liver cancer.

PubMed 2024/11/06(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

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中文摘要

尽管ADAM9上调与多种癌症进展相关,但目前尚缺乏泛癌分析来总结ADAM9的mRNA和蛋白稳定性总体变化,以及其对免疫细胞谱系调控和肿瘤微环境(TME)检查点的致癌作用。

因此,本研究全面分析不同癌症中ADAM9表达的作用及其预后价值,以弥补这一空白。我们利用癌症基因组图谱(TCGA)、基因型-组织表达(GTEx)和临床蛋白质组肿瘤分析联盟(CPTAC)等多个生物信息学数据库,评估ADAM9的基因改变、磷酸化和甲基化,并鉴定与ADAM9高度正相关、可能与其关键互作的基因,采用基因本体(GO)分析探讨其分子功能。

我们还评估高ADAM9表达与重要免疫调节基因及免疫浸润的关系;尤其在肝癌发生过程中,ADAM9可能通过剪切MICA并增加Treg浸润,降低NK细胞效应功能。对90份病理确诊样本进行免疫组织化学(IHC)染色,证实ADAM9表达与肿瘤分期呈正相关,并证明ADAM9相关基因(SNX9、APP、TNF、CDH1、ITGAV和MAD2L2)在HCC发生过程中表达较高。

总之,这项泛癌研究全面阐明ADAM9在多种肿瘤中的预后价值,强调应将其作为一种创新治疗策略加以考虑,尤其是在肿瘤免疫领域。

展开英文摘要原文

A pan-cancer analysis summarizing the overall changes in mRNA and protein stability of ADM9, as well as its oncogenic function on immune cell line modulation and checkpoints within the tumor microenvironment (TME), is lacking, despite the fact that ADM9 up-regulation is correlated with the progression of many cancers.

Therefore, in this study, we comprehensively analyzed the role of ADAM9 expression and its prognostic value in different cancers to fill this gap. Multiple bioinformatics databases such as Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to evaluate the ADAM9 genetic alternation, phosphorylation, and methylation, and indicated highly positive correlated genes that might play a critical interaction with ADAM9 and their molecular function with GO analysis.

We also evaluate the effect of higher ADAM9 with prominent immune modulatory genes and immune infiltration especially in liver cancer pathogenesis stimulates lower NK cell effector functions based on its role in MICA shedding and increasing the Tregs infiltration. Immunohistochemistry (IHC) staining from 90 pathologically verified samples proved the positive correlation between ADAM9 and tumor stages and proved the higher expression of ADAM9 correlated genes (SNX9, APP, TNF, CDH1, ITGAV, MAD2L2) in HCC pathogenesis.

In conclusion, this pan-cancer study provides a comprehensive understanding of the prognostic value of ADAM9 in various tumors emphasizing its importance to be considered as an innovative treatment approach, especially in tumor immunity shortly.

论文信息

作者
AmeliMojarad M、AmeliMojarad M、Wang J、Tavakolpour V、Shariati P
第一作者单位
Department of Bioprocess Engineering, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Mandanalee13@gmail.com.Iran
通讯作者单位
Department of Bioprocess Engineering, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. shariati@nigeb.ac.ir.Iran
期刊
Scientific reports2024 Nov 6
原文标识
PubMed 39505907 · DOI 10.1038/s41598-024-76049-x