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共表达基因增强乳腺癌患者受体状态鉴定的准确性。

Co-expressed genes enhance precision of receptor status identification in breast cancer patients.

机构信息

Section of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems (CeMSIIS), Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.

Translational Gynecology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

出版信息

Breast Cancer Res Treat. 2018 Nov;172(2):313-326. doi: 10.1007/s10549-018-4920-x. Epub 2018 Aug 16.


DOI:10.1007/s10549-018-4920-x
PMID:30117066
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6208909/
Abstract

PURPOSE: Therapeutic decisions in breast cancer patients crucially depend on the status of estrogen receptor, progesterone receptor and HER2, obtained by immunohistochemistry (IHC). These are known to be inaccurate sometimes, and we demonstrate how to use gene-expression to increase precision of receptor status. METHODS: We downloaded data from 3241 breast cancer patients out of 36 clinical studies. For each receptor, we modelled the mRNA expression of the receptor gene and a co-gene by logistic regression. For each patient, predictions from logistic regression were merged with information from IHC on a probabilistic basis to arrive at a fused prediction result. RESULTS: We introduce Sankey diagrams to visualize the step by step increase of precision as information is added from gene expression: IHC-estimates are qualified as 'confirmed', 'rejected' or 'corrected'. Additionally, we introduce the category 'inconclusive' to spot those patients in need for additional assessments so as to increase diagnostic precision and safety. CONCLUSIONS: We demonstrate a sound mathematical basis for the fusion of information, even if partly contradictive. The concept is extendable to more than three sources of information, as particularly important for OMICS data. The overall number of undecidable cases is reduced as well as those assessed falsely. We outline how decision rules may be extended to also weigh consequences, being different in severity for false-positive and false-negative assessments, respectively. The possible benefit is demonstrated by comparing the disease free survival between patients whose IHC could be confirmed versus those for which it was corrected.

摘要

目的:乳腺癌患者的治疗决策取决于免疫组织化学(IHC)获得的雌激素受体、孕激素受体和 HER2 的状态。这些结果有时并不准确,我们展示了如何使用基因表达来提高受体状态的准确性。

方法:我们从 36 项临床研究中下载了 3241 名乳腺癌患者的数据。对于每个受体,我们通过逻辑回归对受体基因和共基因的 mRNA 表达进行建模。对于每个患者,逻辑回归的预测结果与 IHC 的信息以概率为基础合并,得出融合预测结果。

结果:我们引入了桑基图来直观地展示随着基因表达信息的增加,精度逐步提高的过程:IHC 估计被定性为“确认”、“拒绝”或“修正”。此外,我们引入了“不确定”类别,以发现那些需要进一步评估的患者,以提高诊断精度和安全性。

结论:我们证明了融合信息的合理数学基础,即使信息部分相互矛盾。该概念可扩展到三个以上信息源,这对于 OMICS 数据尤为重要。未决病例的总数以及错误评估的病例数都减少了。我们概述了如何扩展决策规则以权衡后果,假阳性和假阴性评估的后果分别不同。通过比较 IHC 可确认的患者与 IHC 可修正的患者之间的无病生存情况,证明了这种方法的可能益处。

相似文献

[1]
Co-expressed genes enhance precision of receptor status identification in breast cancer patients.

Breast Cancer Res Treat. 2018-8-16

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
Comparison of central laboratory assessments of ER, PR, HER2, and Ki67 by IHC/FISH and the corresponding mRNAs (ESR1, PGR, ERBB2, and MKi67) by RT-qPCR on an automated, broadly deployed diagnostic platform.

Breast Cancer Res Treat. 2018-8-17

[10]
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引用本文的文献

[1]
Decision Theory versus Conventional Statistics for Personalized Therapy of Breast Cancer.

J Pers Med. 2022-4-2

[2]
Overview of Sankey flow diagrams: Focusing on symptom trajectories in older adults with advanced cancer.

J Geriatr Oncol. 2022-6

[3]
Comprehensive gene cluster analysis of head and neck squamous cell carcinoma TCGA RNA-seq data defines B cell immunity-related genes as a robust survival predictor.

Head Neck. 2022-2

[4]
Decision theory for precision therapy of breast cancer.

Sci Rep. 2021-2-19

[5]
Microarray Normalization Revisited for Reproducible Breast Cancer Biomarkers.

Biomed Res Int. 2020

本文引用的文献

[1]
Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): An Abridged Explanation and Elaboration.

J Natl Cancer Inst. 2018-8-1

[2]
Gene expression information improves reliability of receptor status in breast cancer patients.

Oncotarget. 2017-8-24

[3]
Optimal classifier for imbalanced data using Matthews Correlation Coefficient metric.

PLoS One. 2017-6-2

[4]
Pathological Complete Response to Neoadjuvant Trastuzumab Is Dependent on HER2/CEP17 Ratio in HER2-Amplified Early Breast Cancer.

Clin Cancer Res. 2017-1-31

[5]
Breast cancer.

Lancet. 2016-11-17

[6]
Low Concordance between Gene Expression Signatures in ER Positive HER2 Negative Breast Carcinoma Could Impair Their Clinical Application.

PLoS One. 2016-2-19

[7]
Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

J Clin Oncol. 2016-4-1

[8]
Identification of estrogen-responsive genes based on the DNA binding properties of estrogen receptors using high-throughput sequencing technology.

Acta Pharmacol Sin. 2015-1

[9]
Updated UK Recommendations for HER2 assessment in breast cancer.

J Clin Pathol. 2015-2

[10]
Hormone receptor expression in breast cancer: postanalytical issues.

J Clin Pathol. 2013-3-22

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