Gene classifiers and uses thereof in skin cancers
Disclosed herein, in certain embodiments, are methods of detecting the presence of a skin cancer based on molecular risk factors. In some instances, the skin cancer is cutaneous T cell lymphoma (CTCL). In some cases, the skin cancer is mycosis fungoides (MF) or Sézary syndrome (SS).
1. A method of treating cutaneous T cell lymphoma (CTCL) in a human subject, comprising:
(a) isolating nucleic acids from a skin sample obtained from the subject by applying at least one adhesive patch to a skin region of the subject in a manner sufficient to adhere skin sample cells to the at least one adhesive patch, and removing the at least one adhesive patch from the skin sample in a manner sufficient to retain the adhered skin sample cells to the at least one adhesive patch, wherein the skin sample cells are substantially free of melanocytes;
(b) measuring gene expression levels of at least one target gene comprising LEF1 by contacting the isolated nucleic acids with at least one probe that recognizes nucleic acids corresponding to the at least one target gene, and detecting binding between the nucleic acids corresponding to the at least one target gene and the at least one probe;
(c) determining that gene expression levels of the at least one target gene are increased at least two-fold compared to a control sample;
(d) identifying the skin sample with the at least two-fold increase in gene expression as being from a CTCL lesion based on the determining; and
(e) administering a CTCL treatment comprising a steroid, interferon, chemotherapy, phototherapy, radiation therapy, a bone marrow transplant, or any combination thereof based on the identifying.
2. The method of claim 1 , wherein the nucleic acids comprise mRNA.
3. The method of claim 1 , wherein the cells comprise T cells or components of T cells.
4. The method of claim 1 , wherein the cells comprise keratinocytes.
5. The method of claim 1 , wherein applying the at least one adhesive patch to the skin region of the subject in a manner sufficient to adhere skin sample cells to the at least one adhesive patch, and removing the at least one adhesive patch from the skin sample in a manner sufficient to retain the adhered skin sample cells to the at least one adhesive patch comprises applying a plurality of adhesive patches to the skin region of the subject in a manner sufficient to adhere skin sample cells to each adhesive patch of the plurality of adhesive patches, and removing each adhesive patch of the plurality of adhesive patches from the skin region in a manner sufficient to retain the adhered skin sample cells to each adhesive patch of the plurality of adhesive patches.
6. The method of claim 1 , wherein the skin region comprises a skin lesion.
7. The method of claim 1 , wherein the CTCL comprises mycosis fungoides.
8. The method of claim 1 , wherein the CTCL comprises Sézary syndrome.
9. The method of claim 1 , wherein the gene expression level is increased as least 10 fold compared to a gene expression level of an equivalent gene from a control sample.
10. The method of claim 1 , wherein the at least one target gene further comprises a gene encoding a saposin-like protein, a gene encoding a FYN-binding protein family member, a gene encoding a TEC kinase family member, a gene encoding a STAT, a gene encoding a TRAF3 interacting protein, a gene encoding a CXC chemokine family member, or a combination thereof.
11. The method of claim 1 , wherein the at least one target gene further comprises a first gene encoding a DNA-binding protein and one or more of a gene encoding modulator of cell death, a gene encoding an antimicrobial, a gene encoding a cytokine, a second gene encoding a DNA-binding protein, or a combination thereof.
12. The method of claim 1 , wherein the at least one target gene comprises at least two target genes.
13. The method of claim 1 , wherein the at least one target gene comprises at least three target genes.
14. The method of claim 1 , wherein identifying has a specificity of at least 70%.
15. The method of claim 1 , wherein identifying has a sensitivity of at least 70%.
16. The method of claim 1 , wherein applying the at least one adhesive patch to the skin region does not remove cells from the basal skin layer.
17. The method of claim 1 , wherein applying the at least one adhesive patch to the skin region removes cells no deeper than 100 microns from the skin surface.
18. The method of claim 1 , wherein applying the at least one adhesive patch to the skin region removes no more than five layers from the stratum corneum.