HOXD8 hypermethylation as a fully sensitive and specific biomarker for biliary tract cancer detectable in tissue and bile samples

Background: Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations. Methods: Study design included statistical power and sample size estimation. A genome-wid...

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Autores: Loi, E. (Eleonora)|||/items/042445ed-3e1f-4f0b-b1f6-7cf65da1a4f7, Zavattari, C. (Cesare)|||/items/2e50dfaf-faf9-4e31-afc6-e8686f60b1aa, Tommas, A. (Alessandro)|||/items/f62a70e6-5222-4038-80bf-a606dba29ed4, Moi, L. (Loredana)|||/items/48a085b9-9ed0-4fa9-9387-41385d143d5c, Canale, M. (Matteo)|||/items/cbdbcc0b-9338-4923-a197-588e98b3dee2, Po, A. (Agnese)|||/items/9d58506d-e6e9-4655-8078-22e39bc2d9c9, Sabato, C. (Claudia)|||/items/02ec0d0a-59a6-4985-b3a9-84a464577b29, Vega-Benedetti, A.F. (Ana Florencia)|||/items/ca68bb08-dd21-4db1-b35d-86f5c15fbb17, Ziranu, P. (Pina)|||/items/a3572a91-869a-4c62-a9a3-62880dd1dc4f, Puzzoni, M. (Marco)|||/items/b0951170-3d36-4f10-9981-3238744cd45c, Lai, E. (Eleonora)|||/items/88083fe9-2aa0-4e8c-85d2-3131382016d0, Faloppi, L. (Luca)|||/items/7fdfaaa2-3169-4cfa-a9e7-b44d19b60bec, Rullán, M. (María)|||/items/090adc1a-62be-43ca-8269-a2a28632d772, Amat, I. (Irene)|||/items/739f8272-7546-44c5-99f5-145deaa7c08c, Urman, J.M. (Jesús M.)|||/items/0cf83217-b40d-47b8-898f-d8b73d603cfa, Arechederra, M. (María)|||/items/8db5d239-c664-48b0-9bf7-17aa664dd287, Berasain-Lasarte, C. (Carmen)|||/items/f1d61c19-1753-4442-a3fd-cc90220e84a0, Ferretti, E. (Elisabetta)|||/items/efa4c4d9-2f7d-4091-9526-05fa977e4260, Casadei-Gardini, A. (Andrea)|||/items/80fdaa32-d954-44ea-a9d0-d1fc52de5982, Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f, Alonso, S. (Sergio)|||/items/1a6e10aa-a4cb-4d2d-b497-41909f667936, Scartozzi, M. (Mario)|||/items/edd9c980-72dc-4aba-bca4-84686c6d728c, Zavattari, P. (Patrizia)|||/items/440d9dec-5df3-42d0-a782-dc1ba467485d
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/116687
Acceso en línea:https://hdl.handle.net/10171/116687
Access Level:acceso abierto
Palabra clave:Hepatología
Biliary tract cancers
Biomarker
HOXD8
Descripción
Sumario:Background: Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations. Methods: Study design included statistical power and sample size estimation. A genome-wide methylation study of an explorative cohort (50 BTC and ten matched non-tumoral tissue samples) has been performed. BTC-specific altered CpG islands were validated in over 180 samples (174 BTCs and 13 non-tumoral controls). The final biomarkers, selected by a machine-learning approach, were validated in independent tissue (18 BTCs, 14 matched non-tumoral samples) and bile (24 BTCs, five non-tumoral samples) replication series, using droplet digital PCR. Results: We identified and successfully validated BTC-specific DNA methylation alterations in over 200 BTC samples. The two-biomarker panel, selected by an in-house algorithm, showed an AUC > 0.97. The best-performing biomarker (chr2:176993479-176995557), associated with HOXD8, a pivotal gene in cancer-related pathways, achieved 100% sensitivity and specificity in a new series of tissue and bile samples. Conclusions: We identified a novel fully efficient BTC biomarker, associated with HOXD8 gene, detectable both in tissue and bile by a standardised assay ready-to-use in clinical trials also including samples from non-invasive matrices.

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