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

Sep 21, 2026

Uploaded by Skyler

A pan-cancer analysis addresses the overall changes in ADAM9-related mRNA and protein stability and evaluates its oncogenic role in modulating immune-cell behavior and immune checkpoints within the tumor microenvironment. ADAM9 expression and prognostic value across cancers are assessed using TCGA, GTEx, and CPTAC to examine genetic alterations, phosphorylation, and methylation, supported by correlation and GO analyses. In liver cancer, higher ADAM9 associates with immune modulatory genes and infiltration patterns, including reduced NK effector functions and increased Tregs, confirmed by immunohistochemistry in 90 samples.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Materials and methods

The expression of ADAM9 analysis

Analysis of DNA methylation and protein phosphorylation

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN A pan-cancer study of ADAM9’s immunological function and prognostic value particularly in liver cancer Mandana AmeliMojarad1,5􀀍, Melika AmeliMojarad1,5, Jiang Wang2, Vahid Tavakolpour3,4 & Parvin Shariati1􀀍 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 playa 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. Keywords ADAM9, Biomarker, Immune infiltration, Pan-cancer analysis, Tumor microenvironment Recent years have seen a significant amount of research focused on the application of novel bioinformatics techniques, which, in addition to the standard surgical treatments, chemotherapy, and radiotherapy, opened up new avenues for the identification of prognostic and diagnostic biomarkers that are useful in the treatment of a variety of cancers1–3. To find a biomarker that could be used to forecast clinical prognosis, it is therefore essential to look into the genes associated with tumor growth and development4. A disintegrin and metalloproteinases (ADAMs) family of proteins is important in the proteolytic process involved in different cells interactions5. ADAM9 a member of ADAMs family that was initially discovered in breast cancer in 1996, has been found ina variety of solid tumors, suggesting a crucial role in tumor invasion and metastasis6,7.The abundant expression of ADAM9 is widely reported in human tissues, and multiple immune cell types suggesting its involvement indifferent pathological conditions such as inflammation, degenerative diseases, and tumorigenesis6,8,9.In recent years, different studies discovered the important aspect of ADAM9 in different cancers identifying its great potential to be considered as a prognostic marker10, yet there is no pan-cancer analysis to comprehensively analyse its molecular aberrations and its effect on tumour infiltrating immune cells and tumor microenvironment (TME) . Therefore, in this work we evaluate the ADAM9 alternation across 33 different cancers, and discussedits role on immune checkpoints, immune cell infiltration, molecular pathways, to provide a better direction for 1Department of Bioprocess Engineering, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. 2Department of Bioinformatics, Nanjing Medical University, Nanjing, China. 3Department of Stem Cells and Regenerative Medicine, Faculty of Medical Biotechnology,

FAQs

What question does the pan-cancer study of ADAM9 aim to address?

It targets the lack of pan-cancer understanding of how ADAM9 affects immune-cell modulation and immune checkpoints, and how ADAM9 relates to prognostic value, especially in liver cancer.

Which databases were used to analyze ADAM9 across cancers?

The study uses Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) to evaluate ADAM9 genetic alterations and related molecular features.

How was ADAM9’s relationship with tumor features in liver cancer validated?

Immunohistochemistry on 90 pathologically verified samples showed positive correlations between ADAM9, tumor stages, and ADAM9-associated genes in hepatocellular carcinoma pathogenesis.

Sep 21, 2026

Uploaded by Skyler