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Elevated Levels of SOX10 in Serum from Vitiligo and Melanoma Patients, Analyzed by Proximity Ligation Assay
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.ORCID-id: 0000-0002-5226-1427
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
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2016 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 4, artikel-id e0154214Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
2016. Vol. 11, nr 4, artikel-id e0154214
Nyckelord [en]
sox10 proximity ligation assay
Nationell ämneskategori
Cell- och molekylärbiologi
Identifikatorer
URN: urn:nbn:se:uu:diva-289194DOI: 10.1371/journal.pone.0154214ISI: 000374970600050PubMedID: 27110718OAI: oai:DiVA.org:uu-289194DiVA, id: diva2:924845
Forskningsfinansiär
EU, FP7, Sjunde ramprogrammet, 294409EU, FP7, Sjunde ramprogrammet, 316929VetenskapsrådetTillgänglig från: 2016-04-29 Skapad: 2016-04-29 Senast uppdaterad: 2018-01-10Bibliografiskt granskad
Ingår i avhandling
1. Molecular Tools for Biomarker Detection
Öppna denna publikation i ny flik eller fönster >>Molecular Tools for Biomarker Detection
2017 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2017. s. 48
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1387
Nyckelord
Rolling circle amplification, padlock probe
Nationell ämneskategori
Genetik
Identifikatorer
urn:nbn:se:uu:diva-331745 (URN)978-91-513-0114-3 (ISBN)
Disputation
2017-12-08, BMC/A1:111a, Husargatan 3, Uppsala, 13:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2017-11-14 Skapad: 2017-10-17 Senast uppdaterad: 2018-03-07

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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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Institutionen för immunologi, genetik och patologiScience for Life Laboratory, SciLifeLabMolekylära verktygInstitutionen för radiologi, onkologi och strålningsvetenskapAutoimmunitetDermatologi och venereologi
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