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Elevated Levels of SOX10 in Serum from Vitiligo and Melanoma Patients, Analyzed by Proximity Ligation Assay
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-5226-1427
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 4, e0154214Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 11, no 4, e0154214
Keyword [en]
sox10 proximity ligation assay
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-289194DOI: 10.1371/journal.pone.0154214ISI: 000374970600050PubMedID: 27110718OAI: oai:DiVA.org:uu-289194DiVA: diva2:924845
Funder
EU, FP7, Seventh Framework Programme, 294409EU, FP7, Seventh Framework Programme, 316929Swedish Research Council
Available from: 2016-04-29 Created: 2016-04-29 Last updated: 2017-11-30Bibliographically approved
In thesis
1. Molecular Tools for Biomarker Detection
Open this publication in new window or tab >>Molecular Tools for Biomarker Detection
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The advance of biological research promotes the emerging of new methods and solutions to answer the biological questions. This thesis describes several new molecular tools and their applications for the detection of genomic and proteomic information with extremely high sensitivity and specificity or simplify such detection procedures without compromising the performance.

In paper I, we described a general method namely super RCA, for highly specific counting of single DNA molecules. Individual products of a range of molecular detection reactions are magnified to Giga-Dalton levels that are easily detected for counting one by one, using methods such as low-magnification microscopy, flow cytometry, or using a mobile phone camera. The sRCA-flow cytometry readout presents extremely high counting precision and the assay’s coefficient of variation can be as low as 0.5%. sRCA-flow cytometry readout can be applied to detect the tumor mutations down to 1/100,000 in the circulating tumor cell-free DNA.

In paper II, we applied the super RCA method into the in situ sequencing protocol to enhance the amplified mRNA detection tags for better signal-to-noise ratios. The sRCA products co-localize with primary RCA products generated from the gene specific padlock probes and remain as a single individual object in during the sequencing step. The enhanced sRCA products is 100% brighter than regular RCA products and the detection efficiency at least doubled with preserved specificity using sRCA compared to standard RCA.

In paper III, we described a highly specific and efficient molecular switch mechanism namely RCA reporter. The switch will initiate the rolling circle amplification only in the presence of correct target sequences. The RCA reporter mechanism can be applied to recognize single stranded DNA sequences, mRNA sequences and sequences embedded in the RCA products.

In paper IV, we established the solid phase Proximity Ligation Assay against the SOX10 protein using poly clonal antibodies. Using this assay, we found elevated SOX10 in serum at high frequency among vitiligo and melanoma patients. While the healthy donors below the threshold.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 48 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1387
Keyword
Rolling circle amplification, padlock probe
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-331745 (URN)978-91-513-0114-3 (ISBN)
Public defence
2017-12-08, BMC/A1:111a, Husargatan 3, Uppsala, 13:15 (English)
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Supervisors
Available from: 2017-11-14 Created: 2017-10-17 Last updated: 2017-11-14

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Chen, LeiVuu, JimmyUllenhag, GustavKämpe, OlleLandegren, UlfKamali-Moghaddam, MasoodHedstrand, Håkan

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Chen, LeiVuu, JimmyUllenhag, GustavKämpe, OlleLandegren, UlfKamali-Moghaddam, MasoodHedstrand, Håkan
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Department of Immunology, Genetics and PathologyScience for Life Laboratory, SciLifeLabMolecular toolsDepartment of Radiology, Oncology and Radiation ScienceAutoimmunityDermatology and Venereology
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