Cargando…

Cathepsin W, T-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor K1 are sensitive and specific RNA biomarkers of canine epitheliotropic lymphoma

Cutaneous T-cell lymphoma (CTCL) is an uncommon type of lymphoma involving malignant skin-resident or skin-homing T cells. Canine epitheliotropic lymphoma (EL) is the most common form of CTCL in dogs, and it also spontaneously arises from T lymphocytes in the mucosa and skin. Clinically, it can be d...

Descripción completa

Detalles Bibliográficos
Autores principales: Olayinka, Jadesola Temitope, Nagarkar, Akanksha, Ma, Diana Junyue, Wong, Neil B., Romasco, Andrew, Piedra-Mora, Cesar, Wrijil, Linda, David, Clement N., Gardner, Heather L., Robinson, Nicholas A., Hughes, Kelly L., Barton, Bruce, London, Cheryl A., Almela, Ramón M., Richmond, Jillian M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654980/
https://www.ncbi.nlm.nih.gov/pubmed/38026637
http://dx.doi.org/10.3389/fvets.2023.1225764
_version_ 1785136727680090112
author Olayinka, Jadesola Temitope
Nagarkar, Akanksha
Ma, Diana Junyue
Wong, Neil B.
Romasco, Andrew
Piedra-Mora, Cesar
Wrijil, Linda
David, Clement N.
Gardner, Heather L.
Robinson, Nicholas A.
Hughes, Kelly L.
Barton, Bruce
London, Cheryl A.
Almela, Ramón M.
Richmond, Jillian M.
author_facet Olayinka, Jadesola Temitope
Nagarkar, Akanksha
Ma, Diana Junyue
Wong, Neil B.
Romasco, Andrew
Piedra-Mora, Cesar
Wrijil, Linda
David, Clement N.
Gardner, Heather L.
Robinson, Nicholas A.
Hughes, Kelly L.
Barton, Bruce
London, Cheryl A.
Almela, Ramón M.
Richmond, Jillian M.
author_sort Olayinka, Jadesola Temitope
collection PubMed
description Cutaneous T-cell lymphoma (CTCL) is an uncommon type of lymphoma involving malignant skin-resident or skin-homing T cells. Canine epitheliotropic lymphoma (EL) is the most common form of CTCL in dogs, and it also spontaneously arises from T lymphocytes in the mucosa and skin. Clinically, it can be difficult to distinguish early-stage CTCLs apart from other forms of benign interface dermatitis (ID) in both dogs and people. Our objective was to identify novel biomarkers that can distinguish EL from other forms of ID, and perform comparative transcriptomics of human CTCL and canine EL. Here, we present a retrospective gene expression study that employed archival tissue from biorepositories. We analyzed a discovery cohort of 6 canines and a validation cohort of 8 canines with EL which occurred spontaneously in client-owned companion dogs. We performed comparative targeted transcriptomics studies using NanoString to assess 160 genes from lesional skin biopsies from the discovery cohort and 800 genes from the validation cohort to identify any significant differences that may reflect oncogenesis and immunopathogenesis. We further sought to determine if gene expression in EL and CTCL are conserved across humans and canines by comparing our data to previously published human datasets. Similar chemokine profiles were observed in dog EL and human CTCL, and analyses were performed to validate potential biomarkers and drivers of disease. In dogs, we found enrichment of T cell gene signatures, with upregulation of IFNG, TNF, PRF1, IL15, CD244, CXCL10, and CCL5 in EL in dogs compared to healthy controls. Importantly, CTSW, TRAT1 and KLRK1 distinguished EL from all other forms of interface dermatitis we studied, providing much-needed biomarkers for the veterinary field. XCL1/XCL2 were also highly specific of EL in our validation cohort. Future studies exploring the oncogenesis of spontaneous lymphomas in companion animals will expand our understanding of these disorders. Biomarkers may be useful for predicting disease prognosis and treatment responses. We plan to use our data to inform future development of targeted therapies, as well as for repurposing drugs for both veterinary and human medicine.
format Online
Article
Text
id pubmed-10654980
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-106549802023-01-01 Cathepsin W, T-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor K1 are sensitive and specific RNA biomarkers of canine epitheliotropic lymphoma Olayinka, Jadesola Temitope Nagarkar, Akanksha Ma, Diana Junyue Wong, Neil B. Romasco, Andrew Piedra-Mora, Cesar Wrijil, Linda David, Clement N. Gardner, Heather L. Robinson, Nicholas A. Hughes, Kelly L. Barton, Bruce London, Cheryl A. Almela, Ramón M. Richmond, Jillian M. Front Vet Sci Veterinary Science Cutaneous T-cell lymphoma (CTCL) is an uncommon type of lymphoma involving malignant skin-resident or skin-homing T cells. Canine epitheliotropic lymphoma (EL) is the most common form of CTCL in dogs, and it also spontaneously arises from T lymphocytes in the mucosa and skin. Clinically, it can be difficult to distinguish early-stage CTCLs apart from other forms of benign interface dermatitis (ID) in both dogs and people. Our objective was to identify novel biomarkers that can distinguish EL from other forms of ID, and perform comparative transcriptomics of human CTCL and canine EL. Here, we present a retrospective gene expression study that employed archival tissue from biorepositories. We analyzed a discovery cohort of 6 canines and a validation cohort of 8 canines with EL which occurred spontaneously in client-owned companion dogs. We performed comparative targeted transcriptomics studies using NanoString to assess 160 genes from lesional skin biopsies from the discovery cohort and 800 genes from the validation cohort to identify any significant differences that may reflect oncogenesis and immunopathogenesis. We further sought to determine if gene expression in EL and CTCL are conserved across humans and canines by comparing our data to previously published human datasets. Similar chemokine profiles were observed in dog EL and human CTCL, and analyses were performed to validate potential biomarkers and drivers of disease. In dogs, we found enrichment of T cell gene signatures, with upregulation of IFNG, TNF, PRF1, IL15, CD244, CXCL10, and CCL5 in EL in dogs compared to healthy controls. Importantly, CTSW, TRAT1 and KLRK1 distinguished EL from all other forms of interface dermatitis we studied, providing much-needed biomarkers for the veterinary field. XCL1/XCL2 were also highly specific of EL in our validation cohort. Future studies exploring the oncogenesis of spontaneous lymphomas in companion animals will expand our understanding of these disorders. Biomarkers may be useful for predicting disease prognosis and treatment responses. We plan to use our data to inform future development of targeted therapies, as well as for repurposing drugs for both veterinary and human medicine. Frontiers Media S.A. 2023-11-03 /pmc/articles/PMC10654980/ /pubmed/38026637 http://dx.doi.org/10.3389/fvets.2023.1225764 Text en Copyright © 2023 Olayinka, Nagarkar, Ma, Wong, Romasco, Piedra-Mora, Wrijil, David, Gardner, Robinson, Hughes, Barton, London, Almela and Richmond. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
Olayinka, Jadesola Temitope
Nagarkar, Akanksha
Ma, Diana Junyue
Wong, Neil B.
Romasco, Andrew
Piedra-Mora, Cesar
Wrijil, Linda
David, Clement N.
Gardner, Heather L.
Robinson, Nicholas A.
Hughes, Kelly L.
Barton, Bruce
London, Cheryl A.
Almela, Ramón M.
Richmond, Jillian M.
Cathepsin W, T-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor K1 are sensitive and specific RNA biomarkers of canine epitheliotropic lymphoma
title Cathepsin W, T-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor K1 are sensitive and specific RNA biomarkers of canine epitheliotropic lymphoma
title_full Cathepsin W, T-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor K1 are sensitive and specific RNA biomarkers of canine epitheliotropic lymphoma
title_fullStr Cathepsin W, T-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor K1 are sensitive and specific RNA biomarkers of canine epitheliotropic lymphoma
title_full_unstemmed Cathepsin W, T-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor K1 are sensitive and specific RNA biomarkers of canine epitheliotropic lymphoma
title_short Cathepsin W, T-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor K1 are sensitive and specific RNA biomarkers of canine epitheliotropic lymphoma
title_sort cathepsin w, t-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor k1 are sensitive and specific rna biomarkers of canine epitheliotropic lymphoma
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654980/
https://www.ncbi.nlm.nih.gov/pubmed/38026637
http://dx.doi.org/10.3389/fvets.2023.1225764
work_keys_str_mv AT olayinkajadesolatemitope cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT nagarkarakanksha cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT madianajunyue cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT wongneilb cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT romascoandrew cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT piedramoracesar cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT wrijillinda cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT davidclementn cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT gardnerheatherl cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT robinsonnicholasa cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT hugheskellyl cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT bartonbruce cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT londoncheryla cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT almelaramonm cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma
AT richmondjillianm cathepsinwtcellreceptorassociatedtransmembraneadapter1lymphotactinandkillercelllectinlikereceptork1aresensitiveandspecificrnabiomarkersofcanineepitheliotropiclymphoma