The Role of Transmembrane Mucins in Lung Diseases

Topic Information

Dear Colleagues,

Transmembrane mucins play a key role in the lung, and are mainly implicated in the process of cellular proliferation, growth, and apoptosis, with increased expression in injured or regenerating epithelial cells (e.g., Krebs von den Lungen-6/MUC1, MUC4, and MUC16). Recently, there has been growing interest in the investigation of the diagnostic and prognostic role of mucins in different lung diseases, including interstitial lung disease (ILD) as well as lung cancer and coronavirus disease 2019 (COVID-19). This has highlighted the role of transmembrane mucins in rheumatologic disorders associated with ILD and the need to identify patients with lung involvement because of the inexorably worsening condition of patients with concomitant interstitial lung involvement. Moreover, since the outbreak of the severe acute respiratory syndrome coronavirus-2 pandemic, the usefulness of mucins for monitoring disease severity has been suggested. This Topic calls for original research articles, brief reports, and review articles focusing on the role of transmembrane mucins in the field of lung disorders.

Dr. Miriana D’Alessandro
Dr. Edoardo Conticini
Dr. Elena Bargagli
Dr. Lucia Vietri
Dr. Laura Bergantini
Dr. Donato Lacedonia
Topic Editors

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Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biology biology	4.2	4.0	2012	18.7 Days	CHF 2700
Cancers cancers	5.2	7.4	2009	17.9 Days	CHF 2900
Current Oncology curroncol	2.6	2.6	1994	18 Days	CHF 2200
Diseases diseases	3.7	-	2013	18.8 Days	CHF 1800
International Journal of Environmental Research and Public Health ijerph	-	5.4	2004	29.6 Days	CHF 2500

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Published Papers (3 papers)

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All Biology Cancers Current Oncology Diseases IJERPH

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13 pages, 1646 KiB  

Open AccessArticle

MET Expression Level in Lung Adenocarcinoma Loosely Correlates with MET Copy Number Gain/Amplification and Is a Poor Predictor of Patient Outcome

by Wei Yin, Ming Guo, Zhenya Tang, Gokce A. Toruner, Joanne Cheng, L. Jeffrey Medeiros and Guilin Tang

Cancers 2022, 14(10), 2433; https://doi.org/10.3390/cancers14102433 - 14 May 2022

Cited by 7 | Viewed by 2158

Abstract

MET amplification has been associated with shorter survival in cancer patients, however, the potential correlation of MET overexpression with either MET amplification or patient outcome is controversial. The aim of this study was to address these questions by correlating MET expression level with [...] Read more.

MET amplification has been associated with shorter survival in cancer patients, however, the potential correlation of MET overexpression with either MET amplification or patient outcome is controversial. The aim of this study was to address these questions by correlating MET expression level with MET copy number and patient outcome in a cohort of 446 patients who had a lung adenocarcinoma: 88 with MET amplification, 118 with polysomy 7, and 240 with negative results by fluorescence in situ hybridization. MET expression assessed by immunohistochemistry was semi-quantified by expression level: absent (0+), weak (1+), moderate (2+) and strong (3+); or by H-score: 0–99, 100–199, and ≥200. MET expression level or H-score was positively but weakly correlated with MET copy number or MET/CEP7 ratio. Strong expression of MET (3+ or H-score ≥ 200) was associated with a shorter overall survival, but it was not an independent hazard for survival by multivariant analysis. We conclude that MET expression is loosely correlated with MET copy number gain/amplification. Strong expression of MET does not independently predict patient outcome. Full article

(This article belongs to the Topic The Role of Transmembrane Mucins in Lung Diseases)

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10 pages, 1709 KiB  

Open AccessArticle

Krebs von den Lungen-6 as Disease Severity Marker for COVID-19 Patients: Analytical Verification and Quality Assessment of the Tosoh AIA-360 Compared to Lumipulse G600II

by Miriana d’Alessandro, Laura Bergantini, Dalila Cavallaro, Sara Gangi, Paolo Cameli, Edoardo Conticini, Siena COVID Unit, Bruno Frediani, Francesco Dotta and Elena Bargagli

Int. J. Environ. Res. Public Health 2022, 19(4), 2176; https://doi.org/10.3390/ijerph19042176 - 15 Feb 2022

Cited by 4 | Viewed by 2184

Abstract

Background: Krebs von den Lungen-6 (KL-6) has been proposed as a disease severity marker of COVID-19. All research articles reported the KL-6 assay detected through Fujirebio reagents by Lumipulse G600/G1200 instrument. In the present study, KL-6 assay was analysed through Tosoh AIA-360 and [...] Read more.

Background: Krebs von den Lungen-6 (KL-6) has been proposed as a disease severity marker of COVID-19. All research articles reported the KL-6 assay detected through Fujirebio reagents by Lumipulse G600/G1200 instrument. In the present study, KL-6 assay was analysed through Tosoh AIA-360 and compared with analytical results by Lumipulse G600 in a population of COVID-19 patients. Materials and methods: Sixty-four patients (median age, IQR 67 (58–76) years), all hospitalized for COVID-19 interstitial pneumonia at Siena COVID Unit. KL-6 was measured by two methods, chemiluminescence enzyme immunoassay (CLEIA) and fluorescent enzyme immunoassay (FEIA) method by Lumipulse G600 II and AIA 360 systems, respectively. Results: KL-6 concentrations evaluated by Lumipulse G600II were significantly higher in severe than those in non-severe patients (p < 0.0001) as well as evaluating by AIA360 (p < 0.0001). Receiver operating curve (ROC) curve analysis showed that KL-6 concentrations, by Lumipuse G600II, distinguished severe from non-severe COVID-19 patients with an area under the curve (AUC) of 99.8% and the best cut-off value was 448 U/mL. AUROC between severe and non-severe COVID-19 patients using T0 KL-6 concentrations by AIA360 was 97.4% and the best cut-off value was 398 U/mL. According to T0 KL-6 concentrations in COVID-19 patients, Bland–Altman difference analysis revealed a mean bias of 78 ± 174.8; while using T1 KL-6 concentrations in COVID-19 patients, Bland–Altman difference analysis revealed a mean bias of 48 ± 126 (95% limits of agreement −199–295) between the Lumipulse G600 II and the AIA360 systems. Conclusions: In conclusion, our study demonstrated that CLEIA and FEIA methods for serum KL-6 detection are comparable and reliable. KL-6 was confirmed as an easily detectable and effective biomarker to identify severe COVID-19 patients. Full article

(This article belongs to the Topic The Role of Transmembrane Mucins in Lung Diseases)

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10 pages, 1571 KiB  

Open AccessArticle

KL-6 in ANCA-Associated Vasculitis Patients with and without ILD: A Machine Learning Approach

by Edoardo Conticini, Miriana d’Alessandro, Laura Bergantini, Diego Castillo, Paolo Cameli, Bruno Frediani, Luca Cantarini and Elena Bargagli

Biology 2022, 11(1), 94; https://doi.org/10.3390/biology11010094 - 08 Jan 2022

Cited by 1 | Viewed by 2378

Abstract

Background: ANCA-associated vasculitis (AAV) are small vessel vasculitis distinguished between microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). The former may have interstitial lung disease (ILD) associated with high morbidity and mortality. Here, Krebs von den Lungen-6 (KL-6), a marker of fibrotic ILD, [...] Read more.

Background: ANCA-associated vasculitis (AAV) are small vessel vasculitis distinguished between microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). The former may have interstitial lung disease (ILD) associated with high morbidity and mortality. Here, Krebs von den Lungen-6 (KL-6), a marker of fibrotic ILD, was assessed for distinguishing AAV patients with ILD from those without ILD, and whether its changes over time are correlated with disease activity. Materials and Methods: Thirteen AAV patients (eight females, mean age 61 ± 14.8 years) were enrolled: six MPA and six GPA. Serum samples were assayed for KL-6 concentrations (Fujirebio Europe, Belgium). To investigate potential binary classifiers for diagnosis of AAV-ILD, we constructed a regression decision tree model. Results: Higher serum KL-6 were in AAV-ILD compared with those without ILD (972.8 ± 398.5 vs 305.4 ± 93.9, p = 0.0040). Area under the receiver operating characteristics curve showed 100% of the diagnostic performance of KL-6 for identifying the ILD involvement (accuracy 91.7%) and the best cutoff value of 368 U/mL (sensitivity 100% and specificity 87.5%). The decision tree model showed a 33% improvement in class purity using a cut-off value of 513 U/mL to distinguish AAV patients with and without ILD. Stratifying AAV patients as MPA and GPA with and without ILD considering T0 and T1 KL-6, the model obtained an improvement of 40% for classifying GPA non-ILD with a T0 serum KL-6 cut-off value of 513 U/mL and a T1 KL-6 cut-off of 301 U/mL. A direct correlation was found between serum T0 KL-6 and T0 BVAS (r = 0.578, p = 0.044). Conclusion: Our multicenter study demonstrated KL-6 as a reliable, non-invasive, and easy-to-perform marker of ILD in AAV patients and its helpfulness for disease activity assessment. Changes in serum concentrations of KL-6 over time could be useful for monitoring AAV patients. Further study of KL-6 as a marker of response to therapy during long-term follow-up would also be worthwhile. Full article

(This article belongs to the Topic The Role of Transmembrane Mucins in Lung Diseases)

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