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通过循环游离RNA对胰腺导管腺癌（PDAC）亚型进行微创判定。

Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell-free RNA.

作者信息

Metzenmacher Martin, Zaun Gregor, Trajkovic-Arsic Marija, Cheung Phyllis, Reissig Timm M, Schürmann Hendrik, von Neuhoff Nils, O'Kane Grainne, Ramotar Stephanie, Dodd Anna, Gallinger Steven, Muckenhuber Alexander, Knox Jennifer J, Kunzmann Volker, Horn Peter A, Hoheisel Jörg D, Siveke Jens T, Lueong Smiths S

机构信息

Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Germany.

German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, a partnership between German Cabcer Research Center (DKFZ) and University Hospital Essen, Germany.

出版信息

Mol Oncol. 2025 Feb;19(2):357-376. doi: 10.1002/1878-0261.13747. Epub 2024 Oct 31.

DOI:10.1002/1878-0261.13747
PMID:39478658
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11792997/
Abstract

Pancreatic ductal adenocarcinoma (PDAC) comprises two clinically relevant molecular subtypes that are currently determined using tissue biopsies, which are spatially biased and highly invasive. We used whole transcriptome sequencing of 10 plasma samples with tumor-informed subtypes, complemented by proteomic analysis for minimally invasive identification of PDAC subtype markers. Data were validated in independent large cohorts and correlated with treatment response and patient outcome. Differential transcript abundance analyses revealed 32 subtype-specific, protein-coding cell-free RNA (cfRNA) transcripts. The subtype specificity of these transcripts was validated in two independent tissue cohorts comprising 195 and 250 cases, respectively. Three disease-relevant cfRNA-defined subtype markers (DEGS1, KDELC1, and RPL23AP7) that consistently associated with basal-like tumors across all cohorts were identified. In both tumor and liquid biopsies, the overexpression of these markers correlated with poor survival. Moreover, elevated levels of the identified markers were linked to a poor response to systemic therapy and early relapse in resected patients. Our data indicate clinical applicability of cfRNA markers in determining tumor subtypes and monitoring disease recurrence.

摘要

胰腺导管腺癌（PDAC）包括两种临床上相关的分子亚型，目前通过组织活检来确定，而组织活检存在空间偏差且具有高度侵入性。我们对10份具有肿瘤信息亚型的血浆样本进行了全转录组测序，并辅以蛋白质组分析，以微创方式鉴定PDAC亚型标志物。数据在独立的大型队列中得到验证，并与治疗反应和患者预后相关联。差异转录本丰度分析揭示了32种亚型特异性的蛋白质编码游离RNA（cfRNA）转录本。这些转录本的亚型特异性在分别包含195例和250例病例的两个独立组织队列中得到验证。确定了三种与疾病相关的cfRNA定义的亚型标志物（DEGS1、KDELC1和RPL23AP7），它们在所有队列中均与基底样肿瘤持续相关。在肿瘤活检和液体活检中，这些标志物的过表达均与较差的生存率相关。此外，所确定标志物的水平升高与全身治疗反应不佳以及切除患者的早期复发有关。我们的数据表明cfRNA标志物在确定肿瘤亚型和监测疾病复发方面具有临床适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/e45b00a8d722/MOL2-19-357-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/329abc7db787/MOL2-19-357-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/694b231dacf0/MOL2-19-357-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/e0d128a4ea1e/MOL2-19-357-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/da39c85e2070/MOL2-19-357-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/1446b75ba422/MOL2-19-357-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/e45b00a8d722/MOL2-19-357-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/329abc7db787/MOL2-19-357-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/694b231dacf0/MOL2-19-357-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/e0d128a4ea1e/MOL2-19-357-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/3bacc83841e1/MOL2-19-357-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/da39c85e2070/MOL2-19-357-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/1446b75ba422/MOL2-19-357-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/11792997/e45b00a8d722/MOL2-19-357-g002.jpg

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