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

Kristiani, Erna and Syahruddin, Elisna and Asmarinah, Asmarinah and Rachmadi, Lisnawati and Ham, Maria Fransisca and Zaini, Jamal and Kekalih, Aria and Heriyanto, Didik Setyo and Hidajat, Heriawaty and Gultom, Fajar Lamhot (2024) WNT/β-Catenin signaling pathway and clinicopathological factors in advanced stage non-small cell lung cancer: a multicenter study. Bali Medical Journal (Bali MedJ), 14 (1). pp. 115-121. ISSN 2302-2914

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Abstract

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 NonSmall 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 platinumbased 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. Keywords: CD44, β-catenin, GSK-3β, NSCLC, platinum-based chemotherapy, RECIST.

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