| Added by | pmartino |
|---|---|
| Group name | EquipePM |
| Item Type | Journal Article |
| Title | A Low-Cost Multiplex Biomarker Assay Stratifies Colorectal Cancer Patient Samples into Clinically-Relevant Subtypes |
| Creator | Ragulan et al. |
| Author | Chanthirika Ragulan |
| Author | Katherine Eason |
| Author | Gift Nyamundanda |
| Author | Yatish Patil |
| Author | Pawan Poudel |
| Author | Elisa Fontana |
| Author | Maguy Del Rio |
| Author | Si-Lin Koo |
| Author | Wah Siew Tan |
| Author | Pierre Martineau |
| Author | David Cunningham |
| Author | Iain Tan |
| Author | Anguraj Sadanandam |
| Abstract | Objective: In order to personalise standard therapies based on molecular profiles, we previously classified colorectal cancers (CRCs) into five distinct subtypes (CRCAssigner) and later into four consensus molecular subtypes (CMS) with different prognoses and treatment responses. For clinical application, here we developed a low-cost multiplex biomarker assay. Design: Three cohorts of untreated fresh frozen CRC samples (n=57) predominantly from primary tumours and profiled by microarray/RNA-Seq were analysed. A reduced 38-gene panel (CRCAssigner-38) was selected from the published 786-gene CRCAssigner signature (CRCAssigner-786) using an in-house gene selection approach. A customised NanoString Technologies nCounter platform-based assay (NanoCRCAssigner) was developed for comparison with different classifiers (CMS subtypes), platforms (microarrays and RNA-Seq), and gene sets (CRCAssigner-38 and CRCAssigner-786). Results: NanoCRCAssigner classified samples (n=48; except those showing a mixture of subtypes) into all five CRCAssigner subtypes with overall high concordance across platforms (> 87%) and with CMS subtypes (81%) irrespective of variable tumour cellularity. The association of subtypes with their known molecular (microsatellite-instable and stemness), mutational (KRAS/BRAF), and clinical characteristics (including overall survival) further demonstrated assay validity. To reduce costs, we switched from the standard protocol to a low-cost protocol with a high Pearson correlation co-efficient (0.9) between protocols. Technical replicates were highly correlated (0.98). Conclusion: Here we developed a low-cost and potentially clinically deployable NanoCRCAssigner assay to facilitate prospective validation of (CRCAssigner and potentially CMS) subtypes in clinical trials and beyond. |
| Publication | bioRxiv |
| Pages | 174847 |
| Date | 2017-08-16 |
| Language | en |
| DOI | 10.1101/174847 |
| URL | https://www.biorxiv.org/content/early/2017/08/16/174847 |
| Accessed | 2017/12/08 - 14:04:38 |
| Library Catalog | www.biorxiv.org |
| Rights | © 2017, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution 4.0 International), CC BY 4.0, as described at http://creativecommons.org/licenses/by/4.0/ |
| Tags | original, PBVOL |
| Date Added | 2018/11/29 - 18:56:30 |
| Date Modified | 2021/03/05 - 10:45:01 |
| Notes and Attachments | Full Text PDF (Attachment) Snapshot (Attachment) |
Institut de Recherche en Cancérologie de
