Skin surface gene expression

Author: Dr Ian Katz, Southern Sun Pathology, New South Wales, Australia. DermNet New Zealand Editor in Chief: Adjunct Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. November 2017.


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Introduction 

At present, many clinical diagnoses in dermatology depend on histopathological confirmation, which is subjective and requires surgical biopsy.

Gene expression analysis is more objective and is expected to improve management of tumours and inflammatory dermatoses.

Molecular analysis techniques

Molecular analysis techniques currently depend on tissue obtained from surgical biopsies. They include:

  • Fluorescence in situ hybridisation (FISH)
  • Comparative genomic hybridisation (CGH)
  • Messenger ribonucleic acid (mRNA) expression profiling.

These tests can help predict the behaviour of melanocytic neoplasms, including melanoma.

Tape stripping

Tape stripping can be used to remove epidermal cells from the skin surface.

  • Ribonucleic acid (RNA) can be recovered from cells adherent to the tape.
  • The RNA can be quantified by reverse transcriptase–polymerase chain reaction (RT–PCR) and profiled by DNA microarrays.
  • RNA recovered by tape stripping can accurately convey real time physiology and derive differential expression profiles.

The entire human genome has been screened to determine the differing gene expression between melanoma and other pigmented skin lesions. The expression levels of all 30,000 human genes were measured in melanomas and non-melanoma lesions by sampling the skin with adhesive patches. Using advanced machine-learning statistical analyses, a set of six genes was found whose RNA levels could reliably differentiate between melanoma and other pigmented lesions.

The gene PRAME (preferentially expressed antigen in melanoma) has a role in oncogenesis (the formation of tumours), while the gene LINC00518 (long intergenic non–protein coding RNA 518) is a member of a newly described class of regulatory RNA molecules; both genes are elevated in melanomas compared to the other lesions. The four other genes provide normal values for laboratory processes.

Based on expression profiles of LINC00518 and PRAME in skin-tissue samples obtained via adhesive patch biopsies, a pigmented lesion assay (PLA) was developed (DermTech, Inc., California, USA). A large validation study including 555 patients established that the PLA can accurately classify pigmented skin lesions with a sensitivity of 92% and a specificity of 69%. After incorporating use of the PLA, dermatologists improved their mean biopsy sensitivity from 95.0% to 98.6% (p = 0.01) in suspected melanoma, while specificity increased from 32.1% to 56.9% (p < 0.001).

Gene expression assays

Gene expression assays are being developed to identify cytokine inflammatory profiles from samples collected using adhesive patches. 

  • Cytokines are released by autoimmune responses in inflammatory diseases such as psoriasis, atopic dermatitis, and cutaneous lupus erythematosus.
  • The biological drugs used to treat inflammatory diseases target specific cytokines.
  • Changes in gene expression can identify patients with a specific cytokine profile that may respond to a particular type of drug therapy.
  • Gene expression can be used to monitor response to therapy and potentially predict flare-ups in patients.

Other uses for gene expression assays

A “Response TNF” product has been proposed that would help monitor patients on biological therapy for psoriasis and determine when a change in therapy is needed.

A “Cytokine Ex 17” product that measures gene expression changes of the interleukin (IL)-17 pathway, including TNF-alpha and IL-23, and could be used as a biomarker for clinical trials and to assess the cytokine status of a patient’s skin.

There are also clinical trials are underway to validate a gene expression test to detect cutaneous squamous cell carcinoma and basal cell carcinoma by using skin samples collected with an adhesive patch skin-biopsy kit.

More applications of the technology are under development. 

Summary

Differential gene expression can be detected via skin surface tape stripping to assist in the diagnosis of melanoma, non-melanoma skin cancer and inflammatory skin disease.

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References 

  • Ferris LK, Jansen B, Ho J, et al. Utility of a noninvasive 2-gene molecular assay for cutaneous melanoma and effect on the decision to biopsy. JAMA Dermatol 2017; 153: 675–80. DOI: 10.1001/jamadermatol.2017.0473. PubMed 
  • Gerami P, Yao Z, Polsky D, et al. Development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. J Am Acad Dermatol. 2017; 76(1): 114–120. Journal
  • Morhenn VB, Chang EY, Rheins LA. A noninvasive method for quantifying and distinguishing inflammatory skin reactions. J Am Acad Dermatol 1999; 41 (5 Pt 1): 687–92. PubMed
  • Wachsman W, Morhenn V, Palmer T, et al. Noninvasive genomic detection of melanoma. Br J Dermatol 2011; 164: 797–806. DOI: 10.1111/j.1365-2133.2011.10239.x. PubMed
  • Wong R, Tran V, Morhenn V, et al. Use of RT-PCR and DNA microarrays to characterize RNA recovered by non-invasive tape harvesting of normal and inflamed skin. J Invest Dermatol 2004; 123: 159–67. DOI: 10.1111/j.0022-202X.2004.22729.x. PubMed

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