从患者匹配的新鲜和福尔马林固定石蜡包埋(FFPE)肺癌组织的单细胞 RNA 图谱中稳健地检测临床相关特征。

IF 6.6 2区 医学 Q1 Medicine
Cellular Oncology Pub Date : 2024-08-01 Epub Date: 2024-02-01 DOI:10.1007/s13402-024-00922-0
Alexandra Trinks, Miha Milek, Dieter Beule, Julie Kluge, Stefan Florian, Christine Sers, David Horst, Markus Morkel, Philip Bischoff
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引用次数: 0

摘要

目的:单细胞转录谱分析揭示了术中收集的患者衍生组织中的细胞异质性和临床相关特征。迄今为止,单细胞研究一直受限于前瞻性收集新鲜或低温保存组织的要求。最近的技术发展可以对 FFPE 组织进行单细胞分析,从而克服了这一限制:方法:我们对患者匹配的新鲜、低温保存和存档 FFPE 癌症组织的单细胞图谱进行了基准分析:结果:我们发现,新鲜组织和 FFPE 常规区块可用于单细胞水平临床相关特征的稳健检测。具体来说,新鲜患者组织和相应的FFPE组织块的单细胞图谱可以整合到共同的低维表征中,细胞亚型集群显示了信号通路、标志和临床有用特征的高度相关转录强度,尽管由于技术差异,单个基因的表达各不相同。与新鲜组织相比,FFPE 组织块显示出更高的细胞多样性。相比之下,低温保存组织的单细胞图谱分析在临床环境中容易出现伪影:我们的分析凸显了单细胞图谱分析在分析回顾性和前瞻性收集的病理档案队列中的潜力,并提高了其在转化研究中的适用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Robust detection of clinically relevant features in single-cell RNA profiles of patient-matched fresh and formalin-fixed paraffin-embedded (FFPE) lung cancer tissue.

Robust detection of clinically relevant features in single-cell RNA profiles of patient-matched fresh and formalin-fixed paraffin-embedded (FFPE) lung cancer tissue.

Purpose: Single-cell transcriptional profiling reveals cell heterogeneity and clinically relevant traits in intra-operatively collected patient-derived tissue. So far, single-cell studies have been constrained by the requirement for prospectively collected fresh or cryopreserved tissue. This limitation might be overcome by recent technical developments enabling single-cell analysis of FFPE tissue.

Methods: We benchmark single-cell profiles from patient-matched fresh, cryopreserved and archival FFPE cancer tissue.

Results: We find that fresh tissue and FFPE routine blocks can be employed for the robust detection of clinically relevant traits on the single-cell level. Specifically, single-cell maps of fresh patient tissues and corresponding FFPE tissue blocks could be integrated into common low-dimensional representations, and cell subtype clusters showed highly correlated transcriptional strengths of signaling pathway, hallmark, and clinically useful signatures, although expression of single genes varied due to technological differences. FFPE tissue blocks revealed higher cell diversity compared to fresh tissue. In contrast, single-cell profiling of cryopreserved tissue was prone to artifacts in the clinical setting.

Conclusion: Our analysis highlights the potential of single-cell profiling in the analysis of retrospectively and prospectively collected archival pathology cohorts and increases the applicability in translational research.

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来源期刊
Cellular Oncology
Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
10.40
自引率
1.50%
发文量
0
审稿时长
16 weeks
期刊介绍: The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.
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