Post-translational modifications of vimentin reflect different pathological processes associated with non-small cell lung cancer and chronic obstructive pulmonary disease

Abstract

Introduction: Vimentin has shown to be highly implicated in cancer initiation and progression. Vimentin is often a target of post-translational modifications (PTMs) which can be disease specific, thus targeting these specific modifications can be of high biomarker potential. In this study we set out to evaluate the biological relevance and serum biomarker potential of citrullinated vimentin (VICM) and non-citrullinated vimentin (VIM) in non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD). Methods: A competitive ELISA targeting VIM was developed and quantified in serum from patients with NSCLC and COPD. VIM was compared with levels of VICM in the same indications. Results: VIM was significantly increased in NSCLC (n = 100) compared to healthy controls (n = 67) in two independent cohorts (p = 0.0003 and p < 0.0001). Furthermore, VIM was highly increased in late stages of NSCLC (p = 0.001), however VIM was not increased in COPD patients (n = 10). Contrarily, serum levels of VICM was not increased in late stages of NSCLC, but highly elevated in patients with COPD (p < 0.0001). Conclusions: These findings suggest a biomarker potential of VIM in NSCLC. Our findings also indicate that PTMs of vimentin are highly relevant and that targeting these modifications can have differential biomarker potential.

Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential

“…A follow-up study further assessing PRO-C19 in COPD and other lung disorders such as idiopathic pulmonary fibrosis would be needed to confirm this. Our research group has developed several other ECM protein markers that have shown biological relevance in lung cancer [11,[32][33][34][35][36][37][38]. Future studies should investigate combining PRO-C19 with these markers and other NSCLC biomarkers to improve overall accuracy.…”

Noninvasive prognostic biomarker potential of quantifying the propeptides of Type XI collagen alpha‐1 chain (PRO‐C11) in patients with pancreatic ductal adenocarcinoma

“…In addition, our group has recently showed the importance of targeting specific PTMs of Type IV collagen and vimentin in metastatic melanoma and lung cancer. We demonstrated that two different neo‐epitopes on the same protein (Type IV collagen and vimentin) could in fact provide opposite prognostic value 37,38 . These data underline the importance of targeting the relevant epitope in cancer biomarker discovery.…”

“…We demonstrated that two different neo-epitopes on the same protein (Type IV collagen and vimentin) could in fact provide opposite prognostic value. 37,38 These data underline the importance of targeting the relevant epitope in cancer biomarker discovery. Furthermore, it urges for caution when targeting the full-length protein, instead of targeting protein fragments as also suggested by Hosein et al 6 In our study, we observed that targeting two different neo-epitopes located in the propeptide of Type XI collagen had completely differential biomarker value.…”

Pathophysiological Role of Vimentin Intermediate Filaments in Lung Diseases

“…Interestingly, the immunogenic properties of Cit-Vim peptides are being explored to develop an anti-cancer vaccine ( Brentville et al, 2020 ). In recent studies, the pathological role of Cit-Vim in chronic lung diseases like COPD, pulmonary fibrosis, and sarcoidosis have been explored ( Vassallo et al, 2014 ; Lugli et al, 2015 ; Ytterberg et al, 2015 ; Musaelyan et al, 2018 ; Nissen et al, 2019 ; Li et al, 2021 ).…”

“…These multiple forms of Vimentin intermediate filaments are comprehensively shown to be involved in inflammation ( Benes et al, 2006 ; Dos Santos et al, 2015 ; Lam et al, 2018 ; Yu et al, 2018 ; Lam et al, 2020 ), and host-pathogen interactions ( Garg et al, 2006 ; Babrak et al, 2015 ; Mahesh et al, 2016 ; Yu et al, 2016 ; Zhang et al, 2020 ) in non-malignant acute lung injuries (trauma, viral infections, bacterial infections, etc.) 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 ).…”