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Oncotype DX 乳腺癌复发评分通过 RT-Profiler Multiplex RT-PCR 检测存在实验间可重复性问题。

Oncotype DX Breast Cancer recurrence score resists inter-assay reproducibility with RT-Profiler Multiplex RT-PCR.

机构信息

Kliniken der Stadt Köln gGmbH, Klinikum der Privaten Universität Witten/Herdecke, Institut für Pathologie, Ostmerheimer Str. 200, D-51109, Köln, Germany.

Kliniken der Stadt Köln gGmbH, Brustzentrum, Neufelder Str. 34, D-51067, Köln, Germany.

出版信息

Sci Rep. 2019 Dec 30;9(1):20266. doi: 10.1038/s41598-019-56910-0.

Abstract

The Oncotype Dx assay is frequently used to test if breast cancer patients can be spared from chemotherapy without negative effects for their future clinical course. However, due to conflicting data on the assay utility, in the recent past its reimbursement situation in Germany was revised; due to continued requests by clinicians for predictive values, our group decided to implement an Oncotype Dx like alternative assay with the objective of obtaining quality and cost optimization. Customized RT-Profiler assays covering the 21 gene panel of the Oncotype Dx assay were applied to a pilot cohort of breast cancer patients with known Oncotype Dx Recurrence Score (RS). The Ct values obtained with RT-Profiler-assays were used to calculate the unscaled Recurrence Score (RSu) values and the thereon based RS according to the Oncotype DX assay rules if available. Despite consistent assay performance it was impossible to establish correlations between RT-Profiler recurrence scores with the respective Oncotype DX values not to mention exact matches. By following the Oncotype DX assay and its interpretation as close as possible we faced several obstructions such as lack of information on RNA amount used, missing units in the single gene expression report, missing references cited in the original study that should explain the determination of the recurrence score formula, and vague information on the normalization of the gene expression impeding the reproduction of Oncotype Dx results in other laboratories. Unfortunately, the Oncotype Dx assay cannot be confirmed by the customized RT-profiler assay, not least because of the fact that the individual gene measurements are not provided in the medical report, although these are mandatory for the RS calculation. In fact, the "single gene report" only contains unscaled scores of the ER, PR, and Her2 genes without any internationally accepted unit used to describe a transcript quantity. Therefore a direct comparison with the in-house measurement to evaluate its performance is impossible. With regard to our findings and the fact that the Oncotype RS represents a likelihood of the risk of relapse it thus remains impossible to assess the clinical necessity of this assay.

摘要

Oncotype Dx 检测常用于测试乳腺癌患者是否可以避免化疗而不会对其未来的临床过程产生负面影响。然而,由于该检测的效用存在相互矛盾的数据,在最近,德国对其报销情况进行了修订;由于临床医生继续要求预测值,我们的小组决定实施一种类似于 Oncotype Dx 的替代检测,以实现质量和成本的优化。针对具有已知 Oncotype Dx 复发评分 (RS) 的乳腺癌患者的试点队列,应用了涵盖 Oncotype Dx 检测 21 个基因的定制 RT-Profiler 检测。使用 RT-Profiler 检测获得的 Ct 值用于计算未缩放的复发评分 (RSu) 值,并根据可用的 Oncotype DX 检测规则计算基于此的 RS。尽管检测性能一致,但仍不可能建立 RT-Profiler 复发评分与相应的 Oncotype DX 值之间的相关性,更不用说精确匹配了。通过尽可能紧密地遵循 Oncotype DX 检测及其解释,我们面临了几个障碍,例如缺乏有关所用 RNA 量的信息、单个基因表达报告中缺少单位、原始研究中缺失应解释复发评分公式确定的引用参考文献,以及关于基因表达标准化的模糊信息,这些信息阻碍了在其他实验室中复制 Oncotype DX 结果。不幸的是,定制的 RT-profiler 检测无法证实 Oncotype Dx 检测,这主要是因为尽管 RS 计算需要,但在医疗报告中并未提供个别基因测量值。实际上,“单个基因报告”仅包含 ER、PR 和 Her2 基因的未缩放评分,而没有用于描述转录物数量的国际公认单位。因此,不可能直接与内部测量值进行比较来评估其性能。鉴于我们的发现以及 Oncotype RS 代表复发风险的可能性,因此仍然不可能评估该检测的临床必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e57e/6937305/388efd950220/41598_2019_56910_Fig1_HTML.jpg

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