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

IF 3.8 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Scientific Reports Pub Date : 2024-11-06 DOI:10.1038/s41598-024-76049-x

Mandana AmeliMojarad, Melika AmeliMojarad, Jiang Wang, Vahid Tavakolpour, Parvin Shariati

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Abstract

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.

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关于 ADAM9 的免疫功能和预后价值（尤其是在肝癌中）的泛癌症研究。

尽管ADM9的上调与许多癌症的进展相关，但目前还缺乏对ADM9的mRNA和蛋白稳定性的整体变化及其对肿瘤微环境（TME）中免疫细胞系调节和检查点的致癌功能的泛癌症分析。因此，在本研究中，我们全面分析了ADAM9在不同癌症中的表达作用及其预后价值，以填补这一空白。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了ADAM9的基因变异、磷酸化和甲基化，并通过GO分析指出了可能与ADAM9起关键作用的高正相关基因及其分子功能。我们还根据ADAM9在MICA脱落和增加Tregs浸润中的作用，评估了ADAM9越高，其免疫调节基因和免疫浸润越显著，尤其是在肝癌发病机制中，会刺激NK细胞效应功能降低。90 份病理样本的免疫组织化学（IHC）染色证明了 ADAM9 与肿瘤分期之间的正相关性，并证明了 ADAM9 相关基因（SNX9、APP、TNF、CDH1、ITGAV、MAD2L2）在 HCC 发病机制中的高表达。总之，这项泛癌症研究全面了解了ADAM9在各种肿瘤中的预后价值，强调了其作为一种创新治疗方法的重要性，尤其是在肿瘤免疫方面。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

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