Serum expression of Vascular Endothelial-Cadherin, CD44, Human High mobility group B1, Kallikrein 6 proteins in different stages of laryngeal intraepithelial lesions and early glottis cancer

PeerJ. 2022 Apr 19:10:e13104. doi: 10.7717/peerj.13104. eCollection 2022.

Abstract

Background: The study was designed to evaluate the potential validity and utility of selected molecular markers in serum samples from patients with specific stages of laryngeal intraepithelial lesions that could serve as diagnostic tools in differentiation of benign and dysplastic lesions from invasive pathologies.

Methods: Prospective study included 80 consecutive patients with vocal fold lesions treated at the single otorhinolaryngology centre. All participants had surgical resection of the lesion. Blood samples were collected from each patient before the surgery. Final diagnosis was confirmed on histopathological examination and included 39 (48.75%) non-dysplastic lesions, eight (10%) low-grade dysplasia, six (7.5%) high-grade dysplasia and 27 (33.75%) invasive cancers. The ELISA procedures were performed according to the manufacturer's instruction. Individual serum concentration of selected proteins was reported in ng/ml: Vascular Endothelial-Cadherin Complex (VE-cad), CD44, Human High mobility group protein B1(HMGB1), Kallikrein 6.

Results: The highest mean levels of HMGB1, KLK6 and VE-cad were detected in sera of patients with low-grade dysplasia (81.14, 24.33, 14.17 respectively). Soluble CD44 was the most elevated in patients with non-dysplastic lesions (2.49). The HMGB1, KLK6 and VE-cad serum levels were increasing from non-dysplastic to low-grade dysplasia and followed by the decrease for high-grade dysplasia and invasive cancer, however the differences were not significant (p-values 0.897, 0.354, 0.1 respectively). Patients' serum had the highest CD44 concentration in non-dysplastic and low-grade dysplasia with the following decrease through high-grade dysplasia and invasive cancer. GERD symptomatic patients had higher levels of KLK6 and CD44 than other patients (p-value 0.06 and 0.084 respectively). There were no significant differences of biomarkers levels related to patients' gender (p-value from 0.243 to 1) or smoking status (p-value from 0.22 to 0.706).

Conclusions: VE-cad, HMGB1, CD44 and KLK6 did not prove to be reliable biomarkers implicating malignant potential within vocal fold hypertrophic intraepithelial lesions.

Keywords: Biomarker; CD44; Dysplasia; Early glottis cancer; Human High mobility group protein B1; Kallikrein 6; Larynx; Vascular Endothelial-Cadherin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Cadherins
  • Glottis / metabolism
  • HMGB1 Protein*
  • Humans
  • Hyaluronan Receptors
  • Hyperplasia / pathology
  • Kallikreins
  • Laryngeal Neoplasms* / metabolism
  • Prospective Studies

Substances

  • HMGB1 Protein
  • Biomarkers
  • Cadherins
  • Kallikreins
  • CD44 protein, human
  • Hyaluronan Receptors

Grants and funding

The study was supported by the internal grant of Medical University of Warsaw (1WF/NM1/18). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.