Academic Journal
44 Liquid biopsy epigenomic profiling for the detection of sarcomatoid renal cell carcinoma
| العنوان: | 44 Liquid biopsy epigenomic profiling for the detection of sarcomatoid renal cell carcinoma |
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| المؤلفون: | Semaan, Karl, Zarif, Talal El, Eid, Marc, Canniff, John, Phillips, Noa, Fortunato, Bard, Savignano, Hunter, Davidson, Matthew P, Chehade, Razane Hajj, Garinet, Simon, Saad, Eddy, Saliby, Renee Maria, Sun, Maxine, Seo, Ji-Heui, Berchuck, Jacob E, Braun, David, Freedman, Matthew L, Choueiri, Toni K, Baca, Sylvan C |
| المصدر: | The Oncologist ; volume 29, issue Supplement_1, page S4-S5 ; ISSN 1083-7159 1549-490X |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2024 |
| الوصف: | Background Sarcomatoid differentiation (SD) in renal cell carcinoma (RCC) is associated with poor survival and heightened response to immune checkpoint blockade. Detection of SD can be challenging due to spatial heterogeneity and sampling error. Herein, we introduce a novel tissue–informed epigenomic approach to noninvasively identify sarcomatoid differentiation in patients with RCC from cell-free DNA (cfDNA) using 1mL of plasma. Methods Chromatin immunoprecipitation and sequencing (ChIP-seq) for H3K27ac – a histone modification associated with active regulatory elements (REs) – was performed on pathologically reviewed clear cell RCC frozen tissue samples with and without SD (sarcomatoid-RCC and epithelioid-RCC, resp.) collected at the Dana-Farber Cancer Institute. Differentially marked REs between sarcomatoid and epithelioid subtypes were identified using DESeq2 (false discovery rate of q < 0.01). After establishing tissue signatures, ChIP-seq was then performed on cell-free chromatin (cfChIP-seq) in plasma from patients with sarc-RCC and epi-RCC. A Sarcomatoid Score was derived for each sample by aggregating the plasma H3K27ac signal at tissue-derived sarcomatoid-specific REs (sarc-REs), while normalizing to signal at epithelioid-specific REs (epi-REs). Scores were compared between the two groups using a Wilcoxon rank-sum test. A classifier was built to distinguish sarc-RCC from epi-RCC based on the Sarcomatoid Score and its performance was evaluated using the area under the receiver operating characteristic (AUROC) curve. Results We identified 25,919 differentially marked REs between 8 sarc-RCC and 8 epi-RCC tissue samples at a false discovery rate of q < 0.01. We selected 12,868 REs that are enriched in sarcomatoid vs. epithelioid. We generated cfChIP-seq profiles from plasma of 29 patients, 17 with sarc-RCC and 12 with epi-RCC. The Sarcomatoid Scores were significantly higher in sarc-RCC vs. epi-RCC plasma samples (p=1.6×10-4; Figure 1A). These scores achieved an AUROC curve of 0.9 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/oncolo/oyae181.006 |
| الاتاحة: | http://dx.doi.org/10.1093/oncolo/oyae181.006 https://academic.oup.com/oncolo/article-pdf/29/Supplement_1/S4/58745360/oyae181.006.pdf |
| Rights: | https://creativecommons.org/licenses/by-nc/4.0/ |
| رقم الانضمام: | edsbas.338B2C11 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/oncolo/oyae181.006 |
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