Candidate Angiogenesis-Related Biomarkers in Patients with Laryngeal Carcinoma (AngLaC): A Prospective Cohort Study

Otolaryngol Head Neck Surg. 2023 Jun;168(6):1433-1442. doi: 10.1002/ohn.219. Epub 2023 Jan 29.

Abstract

Objective: Angiogenesis is indeed a vital process in the progression of carcinomas, including that of larynx. Therefore, this study (AngLaC) aimed to identify candidate angiogenesis-related biomarkers in laryngeal carcinoma patients.

Study design: Prospective controlled cohort study.

Setting: Tertiary referral center.

Methods: In silico analyses of angiogenesis-related genes in laryngeal carcinoma were performed to determine candidate biomarkers. Serum levels of candidate biomarkers were determined via enzyme-linked immunosorbent assay in laryngeal carcinoma patients as well as in an age and gender-matched control group. The associations of the biomarkers with clinical parameters were investigated.

Results: The study included 60 laryngeal carcinoma patients and 20 healthy controls. The serum levels of osteopontin, IGFBP-3, VEGF, sVEGFR-1, and VEGFR-2 were significantly higher in the patient group (p < .001, p ≤ .001, p < .001, p < .01, p < .01, respectively). High osteopontin and sVEGFR-1 levels were associated with locoregional-recurrence (p = .024, p = .016, respectively). IGFBP-3 had the highest diagnostic sensitivity (81.4%) and specificity (80%) among the molecules that were investigated (p < .001). High sVEGFR-1 and low VEGFR-2 levels were associated with poor overall-survival (p = .037, p = .027, respectively). High osteopontin and sVEGFR-1 levels were associated with poor disease-specific survival rates (p = .035, p = .018, respectively).

Conclusion: High serum levels of sVEGFR-1 and osteopontin as well as low serum levels of VEGFR-2 proved to be poor prognostic in terms of survival in laryngeal carcinoma. VEGF, sVEGFR1, VEGFR2, IGFBP-3, and osteopontin levels were found to be significantly increased in larynx cancer patients compared to the normal population. Further studies on osteopontin and sVEGFR-1 are required in order to determine their associations with recurrence.

Keywords: IGFBP-3; VEGF; VEGFR-2; angiogenesis; biomarker; in silico; laryngeal cancer; osteopontin; prognosis; sVEGFR-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Biomarkers, Tumor
  • Carcinoma*
  • Cohort Studies
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3
  • Laryngeal Neoplasms*
  • Neoplasm Recurrence, Local
  • Osteopontin
  • Prospective Studies
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2
  • Insulin-Like Growth Factor Binding Protein 3
  • Osteopontin
  • Biomarkers
  • Biomarkers, Tumor