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Krebs von den Lungen 6 (KL-6) is a novel diagnostic and prognostic biomarker in pleural mesothelioma

Stockhammer, Paul ; Baumeister, Hannah ; Ploenes, Till ; Bonella, Francesco ; Theegarten, Dirk ; Dome, Balazs LU ; Pirker, Christine ; Berger, Walter ; Hegedüs, Luca and Baranyi, Marcell , et al. (2023) In Lung Cancer 185.
Abstract

Objectives: Pleural mesothelioma (PM) is a rare disease with dismal outcome. Systemic treatment options include chemotherapy and immunotherapy, but biomarkers for treatment personalization are missing. The only FDA-approved diagnostic biomarker is the soluble mesothelin-related protein (SMRP). Krebs von den Lungen-6 (KL-6) is a human mucin 1 (MUC1) glycoprotein, which has shown diagnostic and prognostic value as a biomarker in other malignancies. The present study investigated whether KL-6 can serve as a diagnostic and/or prognostic biomarker in PM. Materials and methods: Using a fully-automated chemiluminescence enzyme immunoassay (CLEIA) for KL-6 and SMRP, pleural effusion samples from 87 consecutive patients with PM and 25 patients... (More)

Objectives: Pleural mesothelioma (PM) is a rare disease with dismal outcome. Systemic treatment options include chemotherapy and immunotherapy, but biomarkers for treatment personalization are missing. The only FDA-approved diagnostic biomarker is the soluble mesothelin-related protein (SMRP). Krebs von den Lungen-6 (KL-6) is a human mucin 1 (MUC1) glycoprotein, which has shown diagnostic and prognostic value as a biomarker in other malignancies. The present study investigated whether KL-6 can serve as a diagnostic and/or prognostic biomarker in PM. Materials and methods: Using a fully-automated chemiluminescence enzyme immunoassay (CLEIA) for KL-6 and SMRP, pleural effusion samples from 87 consecutive patients with PM and 25 patients with non-malignant pleural disorders were studied. In addition, KL-6 and SMRP levels were determined in corresponding patient sera, and in an independent validation cohort (n = 122). MUC1 mRNA and protein expression, and KL-6 levels in cell line supernatants were investigated in PM primary cell lines in vitro. Results: PM patients had significantly higher KL-6 levels in pleural effusion than non-malignant controls (AUC 0.78, p < 0.0001). Among PM patients, levels were highest in those with epithelioid or biphasic histologies. There was a strong positive correlation between pleural effusion levels of KL-6 and SMRP (p < 0.0001). KL-6 levels in sera similarly associated with diagnosis of PM, however, to a lesser extent (AUC 0.71, p = 0.008). PM patients with high pleural effusion KL-6 levels (≥303 IU/mL) had significantly better overall survival (OS) compared to those with low KL-6 levels (HR 0.51, p = 0.004). Congruently, high tumor cell MUC1 mRNA expression in primary cell lines associated with prolonged corresponding patient OS (HR 0.35, p = 0.004). These findings were confirmed in an independent validation cohort. Conclusion: This is the first study demonstrating KL-6 as a potential novel liquid-based diagnostic and prognostic biomarker in PM.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomarker, KL-6, Mucins, Pleural effusion, Pleural mesothelioma, SMRP
in
Lung Cancer
volume
185
article number
107360
publisher
Elsevier
external identifiers
  • pmid:37713954
  • scopus:85171751120
ISSN
0169-5002
DOI
10.1016/j.lungcan.2023.107360
language
English
LU publication?
yes
id
c365e068-ffe7-4da6-84bb-f3ba3e729621
date added to LUP
2023-12-08 10:49:32
date last changed
2024-04-21 04:47:17
@article{c365e068-ffe7-4da6-84bb-f3ba3e729621,
  abstract     = {{<p>Objectives: Pleural mesothelioma (PM) is a rare disease with dismal outcome. Systemic treatment options include chemotherapy and immunotherapy, but biomarkers for treatment personalization are missing. The only FDA-approved diagnostic biomarker is the soluble mesothelin-related protein (SMRP). Krebs von den Lungen-6 (KL-6) is a human mucin 1 (MUC1) glycoprotein, which has shown diagnostic and prognostic value as a biomarker in other malignancies. The present study investigated whether KL-6 can serve as a diagnostic and/or prognostic biomarker in PM. Materials and methods: Using a fully-automated chemiluminescence enzyme immunoassay (CLEIA) for KL-6 and SMRP, pleural effusion samples from 87 consecutive patients with PM and 25 patients with non-malignant pleural disorders were studied. In addition, KL-6 and SMRP levels were determined in corresponding patient sera, and in an independent validation cohort (n = 122). MUC1 mRNA and protein expression, and KL-6 levels in cell line supernatants were investigated in PM primary cell lines in vitro. Results: PM patients had significantly higher KL-6 levels in pleural effusion than non-malignant controls (AUC 0.78, p &lt; 0.0001). Among PM patients, levels were highest in those with epithelioid or biphasic histologies. There was a strong positive correlation between pleural effusion levels of KL-6 and SMRP (p &lt; 0.0001). KL-6 levels in sera similarly associated with diagnosis of PM, however, to a lesser extent (AUC 0.71, p = 0.008). PM patients with high pleural effusion KL-6 levels (≥303 IU/mL) had significantly better overall survival (OS) compared to those with low KL-6 levels (HR 0.51, p = 0.004). Congruently, high tumor cell MUC1 mRNA expression in primary cell lines associated with prolonged corresponding patient OS (HR 0.35, p = 0.004). These findings were confirmed in an independent validation cohort. Conclusion: This is the first study demonstrating KL-6 as a potential novel liquid-based diagnostic and prognostic biomarker in PM.</p>}},
  author       = {{Stockhammer, Paul and Baumeister, Hannah and Ploenes, Till and Bonella, Francesco and Theegarten, Dirk and Dome, Balazs and Pirker, Christine and Berger, Walter and Hegedüs, Luca and Baranyi, Marcell and Schuler, Martin and Deshayes, Sophie and Bölükbas, Servet and Aigner, Clemens and Blanquart, Christophe and Hegedüs, Balazs}},
  issn         = {{0169-5002}},
  keywords     = {{Biomarker; KL-6; Mucins; Pleural effusion; Pleural mesothelioma; SMRP}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Lung Cancer}},
  title        = {{Krebs von den Lungen 6 (KL-6) is a novel diagnostic and prognostic biomarker in pleural mesothelioma}},
  url          = {{http://dx.doi.org/10.1016/j.lungcan.2023.107360}},
  doi          = {{10.1016/j.lungcan.2023.107360}},
  volume       = {{185}},
  year         = {{2023}},
}