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

• Published in: Bioscience reports Vol. 41; no. 8
• Main Authors: Chen, Yen-Jen, Huang, Ching-Shui, Phan, Nam-Nhut, Lu, Tzu-Pin, Liu, Chih-Yi, Huang, Chi-Jung, Chiu, Jen-Hwey, Tseng, Ling-Ming, Huang, Chi-Cheng
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd The Biochemical Society 27.08.2021; Portland Press Ltd
• Subjects: Algorithms; Assaying; Biomarkers, Tumor - genetics; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer; Cancer therapies; Centroids; Diagnostics & Biomarkers; DNA microarrays; ErbB-2 protein; Female; Gene expression; Gene Expression & Regulation; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Genomes; Growth factors; High-Throughput Nucleotide Sequencing; Humans; Medical prognosis; Metastasis; Nanotechnology; Oligonucleotide Array Sequence Analysis; Oligonucleotides; Omics; Platforms; Predictions; Software; Taiwan; Taxonomy; Transcriptome; Taiwan; oligonucleotide microarray; PAM50; breast cancer; NanoString nCounter; intrinsic subtype; molecular subtyping
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20211428

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.