Eikrem Øystein, Walther Tedd C, Flatberg Arnar, Beisvag Vidar, Strauss Philipp, Farstad Magnus, Beisland Christian, Koch Even, Mueller Thomas F, Marti Hans-Peter
Department of Clinical Medicine, Nephrology, University of Bergen, Bergen, Norway.
Department of Medicine, Haukeland University Hospital, Bergen, Norway.
BMC Nephrol. 2018 Sep 5;19(1):221. doi: 10.1186/s12882-018-1012-4.
Transcriptome analysis is emerging as emerging as a promising tool to enhance precision of diagnosis and monitoring in solid organ transplantation. Clinical progress has however been hampered by the current reliance on samples from core needle biopsies. This proof-of-principle study examined whether fine needle aspirates, being less invasive, permit the ascertainment of the identical molecular information as core biopsies.
We collected fine needles aspirates from various needle sizes (G19, 21, 23, 25) and the corresponding core biopsies (G16 needle) of non-tumor tissue of full nephrectomy specimens from patients suffering from clear cell renal cell carcinoma (n = 11). RNA expression patterns of two gene sets (156 genes) were executed using targeted RNA sequencing in samples from fine needle vs. core needle samples. A subgroup of kidneys (n = 6) also underwent whole transcriptome RNA sequencing from core biopsies of tumor and peri-tumoral normal tissue (Tru Seq RNA Access, Illumina).
Samples from all needle sizes except two G25 aspirates yielded RNA potentially suitable for sequencing of both gene sets. The mRNA expression patterns of the two gene sets were highly correlated between fine needle aspirates (G23) and corresponding (G16) core biopsies (r = 0.985 and 0.982, respectively). This close correlation was further documented by heat map, Principal Component Analyses (PCA) and whole transcription RNA sequencing. The similarity between fine neddle aspirates and core needle biopsies was additionally confirmed in the subgroup with complete RNA sequencing.
Fine needle biopsies yield similar genomic information to core needle biopsies. The less invasive nature of fine needle biopsies may therefore permit more frequent molecular monitoring and a more targeted use of core needle biopsies in native and especially in transplanted kidneys.
转录组分析正逐渐成为一种有前景的工具,可提高实体器官移植诊断和监测的精准度。然而,当前对芯针活检样本的依赖阻碍了临床进展。这项原理验证研究考察了侵入性较小的细针穿刺抽吸物是否能获取与芯针活检相同的分子信息。
我们收集了来自11例透明细胞肾细胞癌患者全肾切除标本非肿瘤组织的不同针径(G19、21、23、25)的细针穿刺抽吸物以及相应的芯针活检样本(G16针)。使用靶向RNA测序对细针与芯针样本中的两组基因(156个基因)的RNA表达模式进行检测。一组亚组肾脏(n = 6)还对肿瘤及肿瘤周围正常组织的芯针活检样本进行了全转录组RNA测序(Tru Seq RNA Access,Illumina)。
除两份G25穿刺抽吸物外,所有针径样本均产生了可能适用于两组基因测序的RNA。两组基因的mRNA表达模式在细针穿刺抽吸物(G23)与相应的(G16)芯针活检样本之间高度相关(分别为r = 0.985和0.982)。热图、主成分分析(PCA)和全转录RNA测序进一步证实了这种密切相关性。在进行了完整RNA测序的亚组中,细针穿刺抽吸物与芯针活检样本之间的相似性也得到了额外证实。
细针活检产生的基因组信息与芯针活检相似。因此,细针活检侵入性较小的特点可能允许更频繁的分子监测,并在天然肾脏尤其是移植肾脏中更有针对性地使用芯针活检。