Department of Bioprocess Engineering, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Department of Bioinformatics, Nanjing Medical University, Nanjing, China.
Sci Rep. 2024 Nov 6;14(1):26862. doi: 10.1038/s41598-024-76049-x.
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.
缺乏对 ADM9 的 mRNA 和蛋白质稳定性的整体变化以及其对肿瘤微环境 (TME) 中免疫细胞系调节和检查点的致癌功能的泛癌症分析，尽管 ADM9 的上调与许多癌症的进展相关。因此，在这项研究中，我们全面分析了 ADAM9 表达及其在不同癌症中的预后价值，以填补这一空白。使用多个生物信息学数据库，如癌症基因组图谱 (TCGA)、基因组织表达 (GTEx) 和临床蛋白质组肿瘤分析联盟 (CPTAC)，评估 ADAM9 的遗传改变、磷酸化和甲基化，并指出可能与 ADAM9 发挥关键相互作用的高度阳性相关基因及其分子功能与 GO 分析。我们还评估了更高 ADAM9 水平对具有显著免疫调节基因的影响以及免疫浸润，特别是在肝癌发病机制中，基于其对 MICA 脱落的作用和增加 Tregs 浸润，刺激更低的 NK 细胞效应功能。来自 90 个经病理证实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关系，并证明了 ADAM9 相关基因 (SNX9、APP、TNF、CDH1、ITGAV、MAD2L2) 在 HCC 发病机制中的更高表达。总之，这项泛癌症研究提供了对 ADAM9 在各种肿瘤中的预后价值的全面理解，强调了将其视为一种创新治疗方法的重要性，尤其是在肿瘤免疫方面。
