Increased expression of FBW7 may improve the prognosis of lung adenocarcinoma after pemetrexed chemotherapy by transforming the epithelial-to-mesenchymal process
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: FBW7 is a tumor suppressor in cancer. However, few studies have examined the role of FBW7 in lung adenocarcinoma (LUAD), especially the relationship between FBW7 and chemotherapy drug resistance in LUAD. This study analyzed the relationship between FBW7 expression and the clinicopathological features of LUAD patients, and investigated the effect of FBW7 on the efficacy of pemetrexed chemotherapy and its relationship with epithelial-to-mesenchymal transformation (EMT). Methods: A total of 101 patients admitted to Zhoushan Hospital from February 2014 to May 2018 who were pathologically diagnosed with LUAD and received pemetrexed chemotherapy were included in the study. Immunohistochemistry (IHC) was used to detect the expression of FBW7 and EMT-related target proteins in the cancer tissues of the patients, and the relationship between FBW7 and the clinicopathological features, prognosis, and EMT of the LUAD patients was analyzed. Results: FBW7 expression was high in 70 LUAD patients and low in 31 LUAD patients. The patients were followed up for 8–112 months. The 5-year progression-free survival (PFS) and overall survival (OS) were significantly higher in the high FBW7 expression group than the low FBW7 expression group (P<0.001). The Cox regression analysis showed that the higher serum carcinoembryonic antigen (CEA) [hazard ratio (HR) =2.818, 95% confidence interval (CI): 1.100–7.223, P=0.03], higher cytokeratin 19 fragment (Cyfra21-1) (HR =3.587, 95% CI: 1.168–11.015, P=0.03), radical surgery (HR =0.044, 95% CI: 0.006–0.307, P=0.002), and FBW7 expression level (HR =6.270, 95% CI: 2.106–18.660, P=0.001) were independent predictors of OS in patients with LUAD receiving pemetrexed chemotherapy. The Spearman correlation analysis showed that the expression of FBW7 was positively correlated with the expression of E-cadherin (rs=0.314, P=0.001), and negatively correlated with the expression of N-cadherin (rs=−0.325, P=0.001). Conclusions: In patients with LUAD receiving pemetrexed chemotherapy, the high FBW7 expression group had a better prognosis than the low FBW7 expression group. Thus, high expression of FBW7 may affect the efficacy of pemetrexed in patients with LUAD through EMT. Our findings may provide new treatment ideas for patients with LUAD who are resistant to pemetrexed.
Source: Journal of Thoracic Disease
Institutions: Zhoushan Hospital, Universitätsmedizin Göttingen
Language: English
Topic: Lung Cancer Research Studies
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4408685200