Dataset Information

Acute myeloid leukemia stratifies as 2 clinically relevant sphingolipidomic subtypes.

ABSTRACT:

SUBMITTER: Paudel BB

PROVIDER: S-EPMC10909712 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Acute myeloid leukemia stratifies as 2 clinically relevant sphingolipidomic subtypes.

Paudel B Bishal BB Tan Su-Fern SF Fox Todd E TE Ung Johnson J Golla Upendarrao U Shaw Jeremy J P JJP Dunton Wendy W Lee Irene I Fares Wisam A WA Patel Satyam S Sharma Arati A Viny Aaron D AD Barth Brian M BM Tallman Martin S MS Cabot Myles M Garrett-Bakelman Francine E FE Levine Ross L RL Kester Mark M Feith David J DJ Claxton David D Janes Kevin A KA Loughran Thomas P TP

Blood advances 20240301 5

PMID: 38170742

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Project description:Objective: In order to personalize 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 an inexpensive multiplex biomarker-based assay.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). An additional cohort of fresh-frozen paraffin embedded (FFPE) samples (n = 24) was subtyped using NanoCRCAssigner as a proof-of-concept. Results: NanoCRCAssigner classified fresh frozen 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). FFPE samples were also successfully classified and showed high reproducibility (0.96).

Dataset Information

Acute myeloid leukemia stratifies as 2 clinically relevant sphingolipidomic subtypes.

Publications

Acute myeloid leukemia stratifies as 2 clinically relevant sphingolipidomic subtypes.

Similar Datasets

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