sIL-2R- an Immuno-biomarker for Prediction of Metastases in Uveal Melanoma

Anticancer Res. 2022 Mar;42(3):1447-1453. doi: 10.21873/anticanres.15615.

Abstract

Background/aim: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. High serum levels of soluble IL-2 receptor (sIL-2R) have been reported in acute inflammations and metastatic cancers. This study evaluated the potential of high/increasing sIL-2R levels in predicting metastases.

Patients and methods: The study included a total of 1,546 sera samples of subjects from three groups: 119 healthy controls (73 subjects), 566 UM 10 year (10y) disease-free (DF) (220 patients), 861 metastatic UM (268 patients). Patients were followed-up biannually with liver ultrasound and liver function tests for the presence of metastases (Mets). Blood samples to measure the levels of sIL-2R were obtained at the time of primary diagnosis, soon after initial treatment (enucleation, brachytherapy), every 6 months, 10 years from diagnosis, at Mets confirmation by CT, and after additional treatments.

Results: Significantly higher sIL-2R levels were detected in the Mets patients compared to healthy controls and 10y DF patients. Compared to the upper limit of the normal levels of sIL-2R, 1,000 U/ml, its levels in metastatic UM were 61%, 25% in 10y DF UM, and 6.25% in the controls. High levels of sIL-2R in metastatic patients, decreased significantly post treatments. Individual kinetics of markers, indicated similar trends of sIL-2R compared to osteopontin and S-Protein 100, predicting metastases, which were confirmed on liver imaging.

Conclusion: Significantly higher sIL-2R levels were evident in all UM patients with Mets. Significant increases in sIL-2R levels on serial evaluations indicated and predicted UM Mets, enabling earlier treatment of Mets, to improve survival.

Keywords: biomarker; metastases prediction; sIL-2R; uveal melanoma.

Publication types

  • Comparative Study

MeSH terms

  • Biomarkers, Tumor / blood*
  • Case-Control Studies
  • Humans
  • Liver Neoplasms / blood*
  • Liver Neoplasms / immunology
  • Liver Neoplasms / secondary
  • Liver Neoplasms / therapy
  • Melanoma / blood*
  • Melanoma / immunology
  • Melanoma / secondary
  • Melanoma / therapy
  • Predictive Value of Tests
  • Prognosis
  • Receptors, Interleukin-2 / blood*
  • Time Factors
  • Up-Regulation
  • Uveal Neoplasms / blood*
  • Uveal Neoplasms / immunology
  • Uveal Neoplasms / pathology
  • Uveal Neoplasms / therapy

Substances

  • Biomarkers, Tumor
  • Receptors, Interleukin-2

Supplementary concepts

  • Uveal melanoma