WNT/β-Catenin signaling pathway and clinicopathological factors in advanced stage non-small cell lung cancer: a multicenter study

Background: This study aimed to assess the association of GSK-3β, β-catenin, and CD44 expressions, which are the molecules involved in the WNT/β-catenin signaling pathway, with clinicopathological profiles and their correlation with the response to platinum-based chemotherapy using Response Evaluation Criteria in Solid Tumors (RECIST) criteria in advanced-stage Non-Small Cell Lung Cancer (NSCLC). Methods: This research is a case-control study where we retrospectively collected data on every patient diagnosed with stage III-IV, adenocarcinoma EGFR-wild type and squamous cell carcinoma (SCC) who underwent three cycles of platinum-based chemotherapy and had their first RECIST evaluation. Immunohistochemical (IHC) staining for GSK-3β, β-catenin, and CD44 was performed on lung biopsy or surgical samples. RECIST statuses were classified as follows: complete response, partial response, and stable disease were considered favorable outcomes, while progressive disease was considered unfavorable. Results: We analyzed 62 samples, including 37 patients with favorable outcomes and 25 patients with unfavorable outcomes. GSK-3β expression was higher in subjects who were male (p = 0,033), had stage III disease (p = 0,031), and had the SCC subtype (p = 0,015). While GSK-3β expression tended to be higher in subjects with unfavorable responses, while β-catenin and CD44 expression tended to be higher in subjects with favorable responses, these differences were not statistically significant. Correlation analysis among GSK-3β, β-catenin, and CD44 revealed no significant linear associations. Conclusion: The WNT/β-catenin signaling pathway has a specific role in advanced-stage NSCLC. These findings emphasize the complex interplay between clinicopathological features and biological marker expression in NSCLC, warranting further investigation to elucidate underlying regulatory mechanisms and potential therapeutic targets.