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DLBCL cell-of-origin by gene expression in FFPET

ABSTRACT: The assignment of diffuse large B-cell lymphoma into cell-of-origin (COO) groups is becoming increasingly important with the emergence of novel therapies that have selective biological activity in germinal center B-cell-like (GCB) or activated B-cell-like (ABC) groups. The LLMPP's Lymph2Cx assay is a parsimonious digital gene-expression (NanoString) based test for COO assignment in formalin-fixed paraffin-embedded tissue (FFPET) routinely produced in standard diagnostic processes. The 20-gene assay was trained using 51 FFPET biopsies; the locked assay was then validated using an independent cohort of 68 FFPET biopsies. Comparisons were made with COO assignment using the original COO model on matched frozen tissue. In the validation cohort the assay was accurate, with only one case with definitive COO being incorrectly assigned, and robust, with >95% concordance of COO assignment between 2 independent laboratories. These qualities, along with the rapid turn-around-time, make Lymph2Cx attractive for implementation in clinical trials and, ultimately, patient management.

ORGANISM(S): Homo sapiens

PROVIDER: GSE53786 | GEO | 2014/01/14

SECONDARY ACCESSION(S): PRJNA232939

REPOSITORIES: GEO

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DLBCL cell-of-origin by gene expression in FFPET

Project description:The assignment of diffuse large B-cell lymphoma into cell-of-origin (COO) groups is becoming increasingly important with the emergence of novel therapies that have selective biological activity in germinal center B-cell-like (GCB) or activated B-cell-like (ABC) groups. The LLMPP's Lymph2Cx assay is a parsimonious digital gene-expression (NanoString) based test for COO assignment in formalin-fixed paraffin-embedded tissue (FFPET) routinely produced in standard diagnostic processes. The 20-gene assay was trained using 51 FFPET biopsies; the locked assay was then validated using an independent cohort of 68 FFPET biopsies. Comparisons were made with COO assignment using the original COO model on matched frozen tissue. In the validation cohort the assay was accurate, with only one case with definitive COO being incorrectly assigned, and robust, with >95% concordance of COO assignment between 2 independent laboratories. These qualities, along with the rapid turn-around-time, make Lymph2Cx attractive for implementation in clinical trials and, ultimately, patient management. The retrospective study included RNA extracted from 119 clinical samples.

2014-01-14 | E-GEOD-53786 | biostudies-arrayexpress

Cell-of-Origin Subtyping Diffuse Large B-Cell Lymphoma (DLCBL) by Using a 32-Gene Expression Assay in Formalin-Fixed Paraffin-Embedded Tissues

Project description:Objection: To evaluate a qPCR-based 32-gene expression assay to determine the cell-of-origin (COO) of diffuse large B-cell lymphoma (DLBCL) with formalin-fixed paraffin-embedded (FFPE) tissue. Methods: The most established subtyping algorithm, the COO model, categorizes DLBCL into activated B-cell (ABC) and germinal center B-cell (GCB)-like subgroups through gene expression profiling. Biopsy of DLBCL patients with paired FFPE and fresh frozen tissue were collected to assign COO based on the immunohistochemistry (IHC) algorithm (Han’s algorithm), qPCR-based 32-gene expression assay (DLBCL-COO assay) and global gene expression profiling with RNA-seq. Results: The DLBCL-COO assay demonstrated a significantly superior concordance of COO determination with the “gold standard” RNA-seq, comparing with the IHC assignment with Han’s algorithm (91.9% versus 77.5%; P = 0.005). Furthermore, overall survival of GCB patients defined by DLBCL-COO assay was superior significantly towards the ABC patients (Figure 2B, P = 0.023). This effect was not seen when tumors were classified by IHC algorithm. Conclusions: The DLBCL-COO assay provides flexibility and accuracy in DLBCL subtype characterization. These subtype distinctions should help guiding prognostic and therapeutic options for the patients in our daily practice.

2020-04-22 | GSE147986 | GEO

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Project description:Background: Radiotherapy is an effective treatment of intermediate/high-risk locally advanced prostate cancer, however,>30% of patients relapse within 5 years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate prognostics assays in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Patients and methods: Independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasis free survival (MFS). Results: Gene expression analysis was carried out in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten-year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients [HR 3.21 (1.35–7.67); P=0.003]. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases [HR 2.71 (1.11–6.63); P=0.030]. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) [HR 3.23 (1.22–8.59); P=0.019] whilst CAPRA itself was not significant [HR 1.88, (0.52–6.77); P=0.332]. Conclusions: The Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients.

2018-07-12 | GSE116918 | GEO

Genetic influences on DNA methylation (mQTL) in pediatric Crohn's disease patients

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2019-08-17 | GSE135905 | GEO

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Project description:Skin gene expression signatures, including intrinsic subset, are associated with skin score/MRSS improvement during mycophenolate mofetil (MMF) treatment. Gene expression and intrinsic subset assignment were measured in SSc patients amd controls at baseline, and from biopsies of MMF-treated patients.

2013-04-09 | E-GEOD-45485 | biostudies-arrayexpress

Gene expression profiling of subclinical acute kidney rejection II

Project description:Sub-clinical acute rejection (subAR) in kidney transplant recipients (KTR) leads to chronic rejection and graft loss. Non-invasive biomarkers are needed to detect subAR. 307 KTR were enrolled into a multi-center observational study. Precise clinical phenotypes (CP) were used to define subAR. Differential gene expression (DGE) data from peripheral blood samples paired with surveillance biopsies were used to train a Random Forests (RF) model to develop a gene expression profile (GEP) for subAR. A separate cohort of paired samples was used to validate the GEP. Clinical endpoints and gene pathway mapping were used to assess clinical validity and biologic relevance. DGE data from 530 samples (130 subAR) collected from 250 KTR yielded a RF model: AUC 0.85; 0.84 after internal validation with bootstrap resampling. We selected a predicted probability threshold favoring specificity and NPV (87% and 88%) over sensitivity and PPV (64% and 61%, respectively). We tested the locked model/threshold on a separate cohort of 138 KTR undergoing surveillance biopsies at our institution (rejection 42; no rejection 96): NPV 78%; PPV 51%; AUC 0.66. Both the CP and GEP of subAR within the first 12 months following transplantation were independently associated with worse graft outcomes at 24 months, including de novo donor-specific antibody (DSA). Serial GEP tracked with response to treatment of subAR. DGE data from both cohorts mapped to gene pathways indicative of allograft rejection.

2018-07-24 | GSE107506 | GEO

Gene expression profiling of subclinical acute kidney rejection I

2018-07-24 | GSE107503 | GEO

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2017-06-12 | PXD004907 | Pride

Integrative analysis of DCE-MRI and gene expression profiles in construction of a gene classifier for assessment of hypoxia-related risk of chemoradiotherapy failure in cervical cancer

Project description:We have previously identified a prognostic 31-gene expression signature in locally advanced cervical cancer that is associated with tumor hypoxia and reflected by the dynamic contrast enhanced magnetic resonance (DCE-MR) image parameter ABrix. To bring the signature closer to clinical use, we here aimed to construct a classifier with key signature genes that retained an association to ABrix and separated the patients into groups with different hypoxia status and chemoradiotherapy outcome. A training cohort of 42 patients and two independent cohorts of 108 and 131 patients were included. Gene expression data were generated from tumor biopsies by two Illumina array generations (WG6, HT12), and for a subset of 74 patients, by the RT-qPCR platform. The amplitude ABrix in the Brix pharmacokinetic model was extracted from DCE-MR images of 64 patients and used as a measure of hypoxia. Different classifiers were constructed in the training cohort. By evaluating their ability to separate the patients correctly according to ABrix, a 6-gene classifier with strong correlation to ABrix was identified. In validation analyses, the classifier separated the patients into two groups with 5-years progression-free survival probabilities of 85% and 60%. Both the prognostic value and ABrix-association were confirmed in an independent cohort, and robustness across array generations and assay platforms was demonstrated. The prognostic value was independent of existing clinical markers. A robust, prognostic hypoxia classifier has been constructed, and might be used alone or combined with DCE-MR imaging to achieve an early indication of a patient’s risk of failure and allocate high risk patients to adjuvant hypoxia-targeted therapy.

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