CD44 and its ligand hyaluronan as potential biomarkers in malignant pleural mesothelioma: evidence and perspectives

Our plain-English summary of CD44 and its ligand hyaluronan as potential biomarkers in malignant pleural mesothelioma: evidence and perspectives, by L. Cortes-Dericks, R.A. Schmid (Respiratory Research, 2017).

The study

• Authors: L. Cortes-Dericks, R.A. Schmid
• Journal: Respiratory Research
• Published: 2017;18(1):58
• Type of article: Review
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare and highly drug resistant tumor arising from the mesothelial surfaces of the lung pleura. The standard method to confirm MPM is the tedious, time-consuming cytological examination of cancer biopsy. Biomarkers that are detectable in pleural effusion or patient serum are reasonable options to provide a faster and noninvasive diagnostic approach. As yet, the current biomarkers for MPM lack specificity and sensitivity to discriminate this neoplasm from other lung tumors. CD44, a multifunctional surface receptor has been implicated in tumor progression in different cancers including MPM. The interaction of CD44 with its ligand, hyaluronan (HA) has demonstrated an important role in modulating cell proliferation and invasiveness in MPM. In particular, the high expression levels of these molecules have shown diagnostic relevance in MPM. This review will summarize the biology and diagnostic implication of CD44 and HA as well as the interaction of both molecules in MPM that will demonstrate their potential as biomarkers. Augmentation of the current markers in MPM may lead to an earlier diagnosis and management of this disease.

In plain English

This article was a narrative review of published research on CD44, a cell-surface receptor, and its main binding partner hyaluronan (HA) as possible biomarkers for malignant pleural mesothelioma (MPM). It did not study asbestos-exposed people itself. Its background stated that MPM arises mainly from chronic exposure to asbestos fibers. The review described laboratory, tissue and pleural-fluid studies by other researchers. One cited study found strong CD44H staining in 75% of MPM specimens compared with 15% of lung adenocarcinomas. Another cited source stated that about 70% of MPM patients have high HA levels in pleural effusions or serum. Other cited work proposed that high pleural-fluid HA is not specific for MPM. Cited studies combining HA with mesothelin, another marker, gave conflicting results. The authors also reported their own unpublished data: 48.5% to 57.6% of cells in three MPM cell lines were CD44-positive. The authors concluded that combining CD44 and HA, or adding them to a panel of markers, may help earlier and more specific diagnosis. They noted that these markers still do not provide diagnostic accuracy and need extensive validation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: narrative review of published literature, with some unpublished data from the authors' own group
• Who was studied: No study population of its own; the review summarized published studies of MPM cell lines, MPM tissues, pleural fluids and patient serum. The authors' unpublished data came from three MPM cell lines (H28, H2052, Meso4).
• Exposure: Not an exposure study. The review concerned the biomarkers CD44 and hyaluronan. The background states that MPM arises mainly from chronic exposure to asbestos fibers; no fiber types are specified.
• Main results:
  • A cited study (Attanoos et al.) reported strong CD44H (CD44s) immunoreactivity in all 20 biopsies of reactive mesothelium, in 75% of MPM specimens, and in only 15% of pulmonary adenocarcinoma specimens.
  • A cited study (Afify et al.) found membranous CD44s staining in 100% of mesothelial hyperplasia, 86% of malignant mesothelioma and 8% of lung adenocarcinomas.
  • According to a cited source, about 70% of MPM patients show high HA levels in pleural effusions or serum.
  • A cited study (Hillerdal et al.) proposed that high HA in pleural fluid is not specific for MPM, because it can also occur in other malignant or benign diseases, and that a low level does not exclude MPM.
  • One cited study found that combining serum mesothelin and HA did not improve diagnostic performance over mesothelin alone.
  • Another cited study (Creaney et al.) reported that combining mesothelin and HA had higher diagnostic capability than effusion mesothelin alone.
  • The authors' unpublished data: CD44-positive cells made up 48.5% of the H28 cell line, 57.6% of H2052 and 50.2% of Meso4.
• The authors' conclusion: The authors concluded that one marker alone is not sufficient to diagnose MPM. Because of the tight association of HA and CD44, they considered that combining the two, or including them in a panel of markers, may serve as an additional tool to aid early and more specific diagnosis of MPM.
• Limitations the authors state:
  • The authors stated that CD44 and HA still do not provide diagnostic accuracy, and that adding CD44 to a combined mesothelin/HA test would need extensive validation.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Pleura, Biopsy, Pleural Effusion, Neoplasm.

Related studies

• Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma — F. Mundt, G. Nilsonne, et al. (2013)
• Synergistic Enhancement of Cellular Uptake With CD44-Expressing Malignant Pleural Mesothelioma by Combining Cationic Liposome and Hyaluronic Acid-Lipid Conjugate — Y. Sakurai, A. Kato, et al. (2019)
• Hyaluronate binding probe and CD44 in the differential diagnosis of malignant effusions: disappointing results in cytology material — A.C. Filie, A. Abati, et al. (1998)
• Serum hyaluronan as a disease marker — T.C. Laurent, U.B. Laurent, et al. (1996)
• Telomerase activity analyzed with TRAP in situ provides additional information in effusions remaining equivocal after immunocytochemistry and hyaluronan analysis — E. Adell, A. Dejmek (2014)
• Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan — F. Gao, J.R. Koenitzer, et al. (2008)

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