Despite significant advances in the treatment of lung cancer (LC), there are no reliable
biomarkers to effectively predict therapy response and overall survival (O/S) in non-small
cell lung cancer (NSCLC) subtypes. While targeted therapies have improved survival
rates in lung adenocarcinoma (LUAD), effective treatment options for lung squamous
cell carcinoma (LUSC) are still limited. Recent evidence indicates that exosome-bound
WNT5A may significantly contribute to disease progression. Our study assessed the
WNT5A protein as a potential biomarker for diagnosing patients and predicting prognosis
to assist in therapy selection.Primary tumor tissue and serum samples were collected
from a cohort of 60 patients with histologically confirmed NSCLC before therapy. Healthy
serum donors served as controls. Exosomes were isolated, then exosome number and size
were measured, and WNT5A protein levels were identified in tissue and in vesicle-free,
vesicle-bound fractions of the serum by ELISA.Extensive statistical analysis (ROC,
AUC, Cox, etc.) revealed that elevated WNT5A levels on the serum-exosome surface correlated
with distant metastasis, advanced disease stage, and lymph node involvement in LUSC
but not in LUAD patients. Moreover, a high WNT5A exosome surface expression was associated
with a poor response to therapy and shorter O/S in LUSC patients. Additionally, serum-exosome
surface + cargo WNT5A content distinguished LUAD and LUSC subtypes.WNT5A, particularly
its serum exosome-bound form, may serve as a valuable biomarker after further validation
for differentiating NSCLC subtypes and predicting disease progression. Importantly,
the information can become available from a simple serum sample at the time of diagnosis.
