Low CTNND2 expression predicts poor prognosis and modulates PD1/PD-L1 immune checkpoint resistance in lung adenocarcinoma via EGFR-AKT/YAP pathway

Lung adenocarcinoma remains one of the leading causes of cancer-related mortality worldwide, with prognosis and therapeutic response varying greatly among patients. In this study, we investigated the expression and clinical significance of CTNND2 in lung adenocarcinoma and its role in modulating response to immune checkpoint therapy. Our data revealed that CTNND2 is downregulated in lung adenocarcinoma tissues compared to normal lung tissues. Low CTNND2 expression was associated with advanced tumor staging and predicted poor overall survival, indicating its potential as a prognostic biomarker. Furthermore, reduced CTNND2 levels correlated with increased tumor proliferation and metastatic potential, suggesting a role in tumor progression. Mechanistically, we found that low CTNND2 expression was linked to elevated PD-L1 expression in cancer cells. This regulation occurs via the EGFR-AKT/YAP signaling pathway, which has been implicated in immune evasion and drug resistance. Importantly, the modulation of PD-L1 expression by CTNND2 suggests that low CTNND2 may exhibit altered sensitivity to PD1/PD-L1 immune checkpoint inhibitors. These findings provide novel insights into the molecular mechanisms underlying lung adenocarcinoma progression and immune escape. In conclusion, CTNND2 is a potential biomarker for prognosis and a therapeutic target to improve responses to immune checkpoint blockade therapy.