Vimentin expression status is a potential biomarker for brain metastasis development in EGFR-mutant NSCLC patients

Abstract

Background: Despite advances in systemic therapy and improvements in survival for advanced epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), brain metastasis (BM) remains a poor outcome. Previous studies on risk factors for BM occurrence included unselected patients and biomarker prediction of BM in these populations were not well studied. We aimed to identify the role of epithelial mesenchymal transition (EMT) marker and clinical factors predicting BM in EGFR-mutant NSCLC patients. Methods: Advanced EGFR-mutant NSCLC patients in the King Chulalongkorn Memorial Hospital from January 2013 to December 2017 were included. Vimentin expression was assessed by immunohistochemistry. The correlation between vimentin expression and factors associated with BM occurrence was analyzed by univariate and multivariate analyses.Results: 304 patients were enrolled. Of these, 149 patients (49%) developed BM. In multivariate analysis, the occurrence of BM was associated with age <60 years, metastatic disease at diagnosis, and 3 or more metastatic sites. Moreover, positive vimentin expression was also found more common in patients with BM than those without BM (52.4% vs. 27.6%, respectively) and predicted overall BM development in EGFRmutant patients (OR 2.53, 95% CI, 1.11-5.77; P=0.027). Overall survival (OS) was shorter in vimentin positive group than in vimentin negative group. Median OS was 20.0 months (95% CI, 14.51-25.51) and 30.9 months (95% CI, 20.99-40.84), respectively (HR, 1.57; P=0.04).Conclusions: Younger patients with EGFR-mutant NSCLC who had high disease burden were more likely to develop BM. Vimentin served as a biomarker for predicting BM and poor prognostic factor in EGFRmutant patients. EMT pathway may be considered as a therapeutic target in these high-risk populations.

Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma

“…Second, the number of samples with enough tissue available to perform IHC was less than expected, and third, some tumor samples were quite old, which could modify the IHC results. However, in relation to this issue, the percentage of Vimentin expression observed in our samples is consistent with that reported in previous studies [ 113 ].…”

“…High levels of Vimentin were associated with lower PFS in our cohort of patients ( Figure 12 b). Previous studies observed that high expression of Vimentin was associated with a poor outcome to first generation EGFR-TKI and the development of brain metastasis in EGFRm NSCLC patients [ 113 , 114 ]. Our findings also revealed that non-expression of CD133 was associated with a poor degree of histological differentiation, progression to the disease, distant metastasis ( Figure 11 ), and a low OS ( Figure 12 a).…”

Pathophysiological Role of Vimentin Intermediate Filaments in Lung Diseases

“…and chronic lung diseases (IPF, autoimmune ILDs, COPD, and asthma) ( Li et al, 2017a ; Musaelyan et al, 2018 ; Nissen et al, 2019 ; Surolia et al, 2019 ; Li et al, 2021 ). Additionally, vimentin is a gold-standard marker of epithelial–to-mesenchymal differentiation during malignancies ( Satelli and Li, 2011 ; Bogush et al, 2020 ), and is also proposed as a diagnostic and prognostic marker in lung cancers ( Rho et al, 2009 ; Dauphin et al, 2013 ; Rodriguez et al, 2013 ; Havel et al, 2015 ; Teocharoen et al, 2021 ).…”

“…Although no direct anti-vimentin molecule is approved for the treatment of any lung disease, there are several clinical trials utilizing interventions that decrease the expression of vimentin. The value of amplified expression of vimentin is recognized as a prognostic marker is critical in non-small cell lung cancer (NSCLC) ( Al-Saad et al, 2008 ; Dauphin et al, 2013 ; Ye et al, 2016 ; Teocharoen et al, 2021 ). The expression levels of vimentin were used as a prognostic indicator for the treatment efficacy for patients with NSCLC with erlotinib, erlotinib/bevacizumab (EB) or cisplatin/gemcitabine/bevacizumab (PGB) ( Richardson et al, 2012 ; Villalobos et al, 2019 ).…”

Radiomic signature accurately predicts the risk of metastatic dissemination in late-stage non-small cell lung cancer

“…NSE, histological type, number of metastatic lymph nodes, and tumor grade were used to construct a nomogram for use in brain metastasis prediction (18). Vimentin expression was also identified as a potential predictor of brain metastasis in EGFR -mutant NSCLC patients (19).…”