Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Loi E

PROVIDER: S-EPMC9174245 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Loi Eleonora E Zavattari Cesare C Tommasi Alessandro A Moi Loredana L Canale Matteo M Po Agnese A Sabato Claudia C Vega-Benedetti Ana Florencia AF Ziranu Pina P Puzzoni Marco M Lai Eleonora E Faloppi Luca L Rullán María M Carrascosa Juan J Amat Irene I Urman Jesús M JM Arechederra Maria M Berasain Carmen C Ferretti Elisabetta E Casadei-Gardini Andrea A Avila Matías A MA Alonso Sergio S Scartozzi Mario M Zavattari Patrizia P

British journal of cancer 20220217 12

<h4>Background</h4>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.<h4>Methods</h4>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 (1 ...[more]

PMID: 35177798

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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