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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, BACKGROUND, METHODS, RESULTS. Meshes: Aged, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, DNA, Neoplasm, Female, Gene Expression Regulation, Neoplastic, Humans, Incidence, Lung, Lung Neoplasms, Male, Mutation, Neoplasm Recurrence, Local, Neoplasm Staging, Retrospective Studies, Signal Transduction, United States, Wnt Proteins.
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Does wnt pathway activation predict increased risk of tumor recurrence in patients with stage I nonsmall cell lung cancer? Context: To determine the incidence of Wnt pathway activation in patients with stage I NSCLC and its influence on lung cancer recurrence. Despite resection, the 5-year recurrence with localized stage I nonsmall cell lung cancer (NSCLC) is 18.4%-24%. Aberrant Wnt signaling activation plays an important role in a wide variety of tumor types. However, there is not much known about the role the Wnt pathway plays in patients with stage I lung cancer. Tumor and normal lung tissues from 55 patients following resection for stage I NSCLC were subjected to glutathione S-transferase (GST) E-cadherin pulldown and immunoblot analysis to assess levels of uncomplexed β-catenin, a reliable measure of Wnt signaling activation. The β-catenin gene was also screened for oncogenic mutations in tumors with activated Wnt signaling. Cancer recurrence rates were correlated in a blinded manner in patients with Wnt pathway-positive and -negative tumors. Tumors in 20 patients (36.4%) scored as Wnt positive, with only 1 exhibiting a β-catenin oncogenic mutation. Patients with Wnt-positive tumors experienced a significantly higher rate of overall cancer recurrence than those with Wnt-negative tumors (30.0% vs. 5.7%, P = 0.02), with 25.0% exhibiting distal tumor recurrence compared with 2.9% in the Wnt-negative group (P = 0.02).
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Wnt pathway activation occurred in a substantial fraction of Stage I NSCLCs, which was rarely due to mutations. Moreover, Wnt pathway activation was associated with a significantly higher rate of tumor recurrence. These findings suggest that Wnt pathway activation reflects a more aggressive tumor phenotype and identifies patients who may benefit from more aggressive therapy in addition to resection. Final Decision: yes