Observational study links ADAM9 expression to survival in lung adenocarcinoma patientsHigh ADAM9 levels linked to worse lung cancer survival in new data

Frontiers in Medicine Published May 25, 2026 DOI ↗ Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

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Key Takeaway

Note that ADAM9 expression correlates with survival and immunosuppression in lung adenocarcinoma.

This research article presents an observational study with in vitro experiments focused on lung adenocarcinoma. The analysis utilized TCGA-LUAD datasets comprising 517 tumor and 59 normal tissues to evaluate ADAM9 expression alongside efferocytosis-related genes. The scope includes patient stratification, predictive modeling, and correlations with the tumor microenvironment.

The study found that eleven ERG signatures, including ADAM9, stratified patients into high- and low-risk groups with significant survival differences. A nomogram integrating ADAM9 and clinical features demonstrated robust predictive accuracy. High ADAM9 expression correlated with immunosuppressive microenvironments characterized by increased M2 macrophages and neutrophils.

In vitro experiments showed that ADAM9 silencing regulated efferocytosis and polarization in M2 macrophages. This intervention subsequently suppressed tumor cell proliferation and migration via the IL-6/STAT3 signaling pathway. The authors note that adverse events and tolerability were not reported, and follow-up duration was not reported. As an observational study, causal conclusions regarding ADAM9 function are limited.

This research article analyzed data from 517 tumor and 59 normal lung adenocarcinoma tissues from the TCGA-LUAD datasets. The study also included in vitro experiments to understand how ADAM9 affects cancer cells and immune cells. Researchers found that high levels of ADAM9 were linked to an immunosuppressive environment with more M2 macrophages and neutrophils. This environment is often associated with worse patient outcomes.

The study grouped patients into high- and low-risk categories based on ADAM9 and other gene signatures. Those in the high-risk group showed significant differences in survival compared to the low-risk group. A tool combining ADAM9 with clinical features showed strong accuracy in predicting patient outcomes.

Lab experiments showed that reducing ADAM9 activity changed how macrophages behave. This change helped suppress the growth and movement of tumor cells by affecting the IL-6/STAT3 signaling pathway. The findings suggest ADAM9 plays a role in how the tumor interacts with the immune system. However, this was an observational study with lab work, not a clinical trial testing a treatment.

What this means for you:

High ADAM9 linked to immunosuppression and worse survival in lung adenocarcinoma based on tissue data and lab experiments.

Study Details

Study typeGuideline

EvidenceLevel 5

PublishedMay 2026

View Original Abstract ↓

ObjectiveLung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, necessitating identification of novel biomarkers for precision therapy. Herein, we aimed to investigate the role of efferocytosis-related genes (ERGs) in LUAD progression, focusing on ADAM9 as a potential prognostic and therapeutic target.MethodsTCGA-LUAD datasets including 517 tumor and 59 normal tissues were applied to perform consensus clustering, LASSO regression, and immune infiltration algorithms. A prognostic model was constructed and validated via survival analysis and nomogram. Single-cell sequencing was performed to analyze the distribution of ADAM9 in tumor microenvironment. Additionally, in vitro experiments were carried out to analyze the biological function of ADAM9 in LUAD progression.ResultsEleven ERG signatures, including ADAM9, stratified patients into high- and low-risk groups with significant survival differences. A nomogram integrating ADAM9 and clinical features demonstrated robust predictive accuracy. High ADAM9 expression correlated with immunosuppressive microenvironments, characterized by increased M2 macrophages, neutrophils. Single−cell analysis identified predominant enrichment of ADAM9 in M2 macrophage subsets. Pseudotime trajectory analysis linked ADAM9 expression to M2 macrophage differentiation, while cell−cell interaction studies revealed ADAM9−high M2 macrophages as key signaling hubs in the tumor microenvironment. In vitro experiments demonstrated that ADAM9 silencing regulated efferocytosis and polarization in M2 macrophages, and subsequently suppressed tumor cell proliferation and migration via the IL-6/STAT3 signaling pathway.ConclusionOur study innovatively constructed a robust prognostic model based on ERG signatures. ERG signatures including ADAM9 not only precisely forecasted the survival outcomes and therapeutic responses of LUAD patients but also comprehensively uncovered the oncogenic role of ADAM9 in promoting tumor progression through multi-dimensional analysis.

Observational study links ADAM9 expression to survival in lung adenocarcinoma patientsHigh ADAM9 levels linked to worse lung cancer survival in new data

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Observational study links ADAM9 expression to survival in lung adenocarcinoma patientsHigh ADAM9 levels linked to worse lung cancer survival in new data

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