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寡核苷酸微阵列和 NanoString nCounter 对乳腺癌内在分类的分子亚型分类

Molecular subtyping of breast cancer intrinsic taxonomy with oligonucleotide microarray and NanoString nCounter.

机构信息

Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.

Division of General Surgery, Department of Surgery, Cathay General Hospital, Taipei, Taiwan.

出版信息

Biosci Rep. 2021 Aug 27;41(8). doi: 10.1042/BSR20211428.

Abstract

Breast cancer intrinsic subtypes have been identified based on the transcription of a predefined gene expression (GE) profiles and algorithm (prediction analysis of microarray 50 gene set, PAM50). The present study compared molecular subtyping with oligonucleotide microarray and NanoString nCounter assay. A total of 109 Taiwanese breast cancers (24 with adjacent normal breast tissues) were assayed with Affymetrix Human Genome U133 plus 2.0 microarrays and 144 were assayed with the NanoString nCounter while 64 patients were assayed for both platforms. Subtyping with the nearest centroid (single sample prediction (SSP)) was performed, and 16 out of 24 (67%) matched normal breasts were categorized as the normal breast-like subtype. For 64 breast cancers assayed for both platforms, 41 (65%, one unclassified by microarray) were predicted with an identical subtype, resulting in a fair κ statistic of 0.60. Taking nCounter subtyping as the gold standard, prediction accuracy was 43% (3/7), 81% (13/16), 25% (5/20), and 100% (20/20) for basal-like, human epidermal growth factor receptor II (HER2)-enriched, luminal A and luminal B subtypes predicted from microarray GE profiles. Microarray identified more luminal B cases from luminal A subtype predicted by nCounter. It is not uncommon to use microarray for breast cancer molecular subtyping for research. Our study showed that fundamental discrepancy existed between distinct GE assays, and cross-platform equivalence should be carefully appraised when molecular subtyping was conducted with oligonucleotide microarray.

摘要

乳腺癌内在亚型是基于预先定义的基因表达(GE)谱和算法(预测分析微阵列 50 基因集,PAM50)来确定的。本研究比较了分子亚型与寡核苷酸微阵列和 NanoString nCounter 检测。共检测了 109 例台湾乳腺癌(24 例伴有相邻正常乳腺组织)的 Affymetrix Human Genome U133 plus 2.0 微阵列和 144 例的 NanoString nCounter,而 64 例患者同时检测了这两种平台。采用最近质心(单样本预测(SSP))进行了分类,24 例(67%)匹配正常乳腺的正常乳腺样亚型。对于 64 例同时检测两种平台的乳腺癌,41 例(65%,1 例微阵列未分类)预测为相同的亚型,kappa 统计值为 0.60。以 nCounter 亚型为金标准,微阵列 GE 图谱预测的基底样、人表皮生长因子受体 II(HER2)富集、管腔 A 和管腔 B 亚型的预测准确率分别为 43%(3/7)、81%(13/16)、25%(5/20)和 100%(20/20)。微阵列从 nCounter 预测的管腔 A 亚型中识别出更多的管腔 B 病例。研究中常用微阵列进行乳腺癌分子亚型分类。我们的研究表明,不同的 GE 检测之间存在根本差异,在使用寡核苷酸微阵列进行分子亚型分类时,应仔细评估跨平台等效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c20b/8385191/e4537a8efb84/bsr-41-bsr20211428-g1.jpg

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