In lung adenocarcinoma, low expression of the cell surface extracellular nucleotidase CD39 is related to immune infiltration and a poor prognosis.

BACKGROUND

Extracellular nucleotidase on the cell surface CD39 plays a crucial role in the tumor microenvironment in the immunosuppressive adenosine pathway. However, the association between CD39 and lung adenocarcinoma has rarely been recorded. This study aimed to explore the involvement of CD39 in the biological processes of lung cancer.

METHODS

First, a prediction model was established by analyzing the expression of CD39 in lung adenocarcinoma and its relationships with clinical evidence of lung adenocarcinoma using The Cancer Genome Atlas (TCGA) and Tumor IMmune Estimation Resource (TIMER) databases. In the TCGA and TIMER databases, the relationship between CD39 and immune cells and the relationship with immune-related expressed genes were studied. Subsequently, using gene set enrichment analysis (GSEA), the potential mechanism of action was investigated.

RESULTS

Lung adenocarcinoma patients with elevated CD39 expression had improved overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). CD39 expression was reduced in lung adenocarcinoma tumor tissue in the TCGA and TIMER databases. The nomogram's C-index was 0.688 (0.665-0.712), indicating some consistency in the prediction model. According to the TIMER and TCGA databases, CD39 expression was strongly connected with several immune cells invading and with immune checkpoint-related markers such as PDCD1, CD274, CTLA-4, and several functional T cells. GSEA revealed that CD39 influences the extracellular matrix, immunological microenvironment, programmed death 1 (PD-1) expression, glucose metabolism, PTEN stability, inflammatory response, and angiogenesis in lung cancer.

CONCLUSIONS

The current study's findings demonstrated that CD39 can be employed as a possible predictive biomarker for lung adenocarcinoma and may enhance the patients' poor prognosis by preventing the immunological escape of tumor cells from the lung adenocarcinoma tumor microenvironment.