Abstract A39: Concordance of 5-hydroxymethylcytosine-modified genes from circulating cell-free DNA and positron emission tomography in multiple myeloma
Notice bibliographique
Résumé
Abstract Background: Positron emission tomography (PET) is one of the current standard-of-care imaging techniques for evaluating extramedullary disease in multiple myeloma (MM); hypermetabolic focal lesions at diagnosis are associated with poor prognosis. Molecular analysis of circulating cell-free DNA (cfDNA) has potential to not only be a noninvasive test for measuring extramedullary disease to complement imaging, but also provide pathobiologic insights. We previously discovered that signatures of the epigenetic modification 5-hydroxyethylcytosine (5hmC) in cfDNA differ between MM and its precursor conditions and predict relapse risk for MM patients at the time of diagnosis. We evaluated differentially modified 5hmC genes between PET-negative and PET-positive patients at the time of MM diagnosis and assessed concordance of the cfDNA 5hmC profiles with PET. Methods: We prospectively enrolled patients with newly diagnosed MM at The University of Chicago Medical Center from 2010 to 2017. Patients enrolled in the study who underwent standard-of-care PET imaging within 30 days of a corresponding blood draw were evaluated. Blood samples were collected and processed immediately to separate plasma. We profiled 5hmC with DNA extracted from ~2 mL of plasma to construct the 5hmC-seal libraries using the nano-hmC-Seal technology, which then underwent next-generation sequencing. 5hmC sequencing data were mapped to the human genome and annotated to ~22,000 gene bodies. We compared genome-wide 5hmC loci between PET-positive and PET-negative patients with MM. We developed an eight gene-based weighted prognostic score (wp-score) for predicting overall survival by applying the elastic net regularization on Cox proportional hazards model. Next, we evaluated concordance between PET results and wp-score. Results: A total of 71 MM patients (age, 61.2±10.65 year; males n=42) had at least one PET scan performed and had cfDNA sequencing data available; 29 (36%) patients had an initial PET positive for MM and the remaining 52 had a negative PET. We found 14 differentially modified 5hmC genes between PET-positive and PET-negative patients at baseline (p<0.005). PET positivity at baseline is associated with poor prognosis for MM. We also found that 9 out of 19 (47%) patients with a positive PET had a high wp-score (i.e., worse survival), while 11 out of 32 patients (34%) with a negative PET had a low-risk wp-score. Conclusions: Differential enrichment of 5hmC-modifications on gene body regions identified from 5hmC profiling of plasma cfDNA at the time of MM diagnosis differentiates patterns of PET imaging and adds complementary prognostic information to PET. These novel findings support the investigation of 5hmC in cfDNA as part of a multimodal approach to enhance prognostication in MM and potentially guide initial therapy. Citation Format: Benjamin Derman, Zhou Zhang, Jason Karpus, Chang Zeng, Elizabeth Stepniak, Diana West-Szymanski, Rudy Chiu, John Spinelli, Chuan He, Jagoda Jasielec, Andrzej Jakubowiak, Wei Zhang, Brian Chiu. Concordance of 5-hydroxymethylcytosine-modified genes from circulating cell-free DNA and positron emission tomography in multiple myeloma [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A39.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».