Elevated Levels of SOX10 in Serum from Vitiligo and Melanoma Patients, Analyzed by Proximity Ligation Assay

PLoS One. 2016 Apr 25;11(4):e0154214. doi: 10.1371/journal.pone.0154214. eCollection 2016.

Abstract

Background: The diagnosis of malignant melanoma currently relies on clinical inspection of the skin surface and on the histopathological status of the excised tumor. The serum marker S100B is used for prognostic estimates at later stages of the disease, but analyses are marred by false positives and inadequate sensitivity in predicting relapsing disorder.

Objectives: To investigate SOX10 as a potential biomarker for melanoma and vitiligo.

Methods: In this study we have applied proximity ligation assay (PLA) to detect the transcription factor SOX10 as a possible serum marker for melanoma. We studied a cohort of 110 melanoma patients. We further investigated a second cohort of 85 patients with vitiligo, which is a disease that also affects melanocytes.

Results: The specificity of the SOX10 assay in serum was high, with only 1% of healthy blood donors being positive. In contrast, elevated serum SOX10 was found with high frequency among vitiligo and melanoma patients. In patients with metastases, lack of SOX10 detection was associated with treatment benefit. In two responding patients, a change from SOX10 positivity to undetectable levels was seen before the response was evident clinically.

Conclusions: We show for the first time that SOX10 represents a promising new serum melanoma marker for detection of early stage disease, complementing the established S100B marker. Our findings imply that SOX10 can be used to monitor responses to treatment and to assess if the treatment is of benefit at stages earlier than what is possible radiologically.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biological Assay
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Cohort Studies
  • Early Diagnosis
  • Female
  • Humans
  • Lymphatic Metastasis
  • Male
  • Melanocytes / metabolism*
  • Melanocytes / pathology
  • Melanoma / blood
  • Melanoma / diagnosis*
  • Melanoma / genetics
  • Melanoma / pathology
  • Middle Aged
  • S100 Calcium Binding Protein beta Subunit / blood
  • S100 Calcium Binding Protein beta Subunit / genetics
  • SOXE Transcription Factors / blood
  • SOXE Transcription Factors / genetics*
  • Sensitivity and Specificity
  • Skin Neoplasms / blood
  • Skin Neoplasms / diagnosis*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Treatment Outcome
  • Vitiligo / blood
  • Vitiligo / diagnosis*
  • Vitiligo / genetics
  • Vitiligo / pathology

Substances

  • Biomarkers, Tumor
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • SOX10 protein, human
  • SOXE Transcription Factors

Grants and funding

The Research Foundation Stiftelsen Onkologiska Klinikens Forskningsfond in Uppsala, Hudfonden, Welanders stiftelse, Hedlunds stiftelse, Selanders stiftelse, the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreements No. 294409 (ProteinSeq) and No. 316929 (GastricGlycoExpolorer) and personnel at Department of Oncology, Uppsala and Department of Dermatology at Landstinget in Gävleborg, for kindly supporting this study. AB was partly supported by the Ludwig institute for cancer research (LICR), Uppsala Branch, Sweden and partly supported by the Uppsala Berzelii Technology Centre for Neurodiagnostics, financed by the Swedish Governmental Agency for Innovation Systems, the Swedish Research Council, and Uppsala University during this work. LEC was partly supported by a LiSUM PhD scholarship.