Portal de investigación
Analytical Validation of Multiplex Biomarker Assay to Stratify Colorectal Cancer into Molecular Subtypes
Fecha de publicación:
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Autores de INCLIVA
Participantes ajenos a INCLIVA
- Ragulan, C
- Eason, K
- Fontana, E
- Nyamundanda, G
- Patil, Y
- Poudel, P
- Lawlor, RT
- Del Rio, M
- Koo, SL
- Tan, WS
- Sclafani, F
- Begum, R
- Mendes, LST
- Martineau, P
- Scarpa, A
- Tan, IB
- Cunningham, D
- Sadanandam, A
Grupos y Plataformas de I+D+i
Abstract
Previously, we classified colorectal cancers (CRCs) into five CRCAssigner (CRCA) subtypes with different prognoses and potential treatment responses, later consolidated into four consensus molecular subtypes (CMS). Here we demonstrate the analytical development and validation of a custom NanoString nCounter platform-based biomarker assay (NanoCRCA) to stratify CRCs into subtypes. To reduce costs, we switched from the standard nCounter protocol to a custom modified protocol. The assay included a reduced 38-gene panel that was selected using an in-house machine-learning pipeline. We applied NanoCRCA to 413 samples from 355 CRC patients. From the fresh frozen samples (n = 237), a subset had matched microarray/RNAseq profiles (n = 47) or formalin-fixed paraffin-embedded (FFPE) samples (n = 58). We also analyzed a further 118 FFPE samples. We compared the assay results with the CMS classifier, different platforms (microarrays/RNAseq) and gene-set classifiers (38 and the original 786 genes). The standard and modified protocols showed high correlation (> 0.88) for gene expression. Technical replicates were highly correlated (> 0.96). NanoCRCA classified fresh frozen and FFPE samples into all five CRCA subtypes with consistent classification of selected matched fresh frozen/FFPE samples. We demonstrate high and significant subtype concordance across protocols (100%), gene sets (95%), platforms (87%) and with CMS subtypes (75%) when evaluated across multiple datasets. Overall, our NanoCRCA assay with further validation may facilitate prospective validation of CRC subtypes in clinical trials and beyond.
© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Datos de la publicación
- ISSN/ISSNe:
- 2045-2322, 2045-2322
- Tipo:
- Article
- Páginas:
- 7665-7665
- PubMed:
- 31113981
Scientific Reports NATURE PUBLISHING GROUP
Citas Recibidas en Web of Science: 33
Documentos
Filiaciones
Proyectos y Estudios Clínicos
CONTRATOS RIO HORTEGA
Investigador Principal: NOELIA TARAZONA LLAVERO
CM15/00246 . INSTITUTO SALUD CARLOS III
Enfermedad mínima residual en cánceres colorrectales de alto riesgo resecados. Valor de las biopsias líquidas en el seguimiento y análisis de la heterogeneidad tumoral.
Investigador Principal: ANDRÉS CERVANTES RUIPEREZ
PI15/02180 . INSTITUTO SALUD CARLOS III . 2016
Cita
Ragulan C,Eason K,Fontana E,Nyamundanda G,Tarazona N,Patil Y,Poudel P,Lawlor RT,Del Rio M,Koo SL,Tan WS,Sclafani F,Begum R,Mendes LST,Martineau P,Scarpa A,Cervantes A,Tan IB,Cunningham D,Sadanandam A. Analytical Validation of Multiplex Biomarker Assay to Stratify Colorectal Cancer into Molecular Subtypes. Sci Rep. 2019. 9. (1):p. 7665-7665. IF:3,998. (1).
Analytical Validation of Multiplex Biomarker Assay to Stratify Colorectal Cancer into Molecular Subtypes. Ragulan C, Eason K, Fontana E, Nyamundanda G, Tarazona N, Patil Y, Poudel P et al. Scientific Reports. 2019 mayo 21. 9 (1):7665-7665. DOI:10.1038/s41598-019-43492-0. PMID:31113981.
