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Clinical testing of transcriptome-wide expression profiles in high-risk localized and metastatic prostate cancer starting androgen deprivation therapy: an ancillary study of the STAMPEDE abiraterone Phase 3 trial.

Gerhardt Attard | Marina Parry | Emily Grist | Larissa Mendes | Peter Dutey-Magni | Ashwin Sachdeva | Christopher Brawley | Laura Murphy | James Proudfoot | Sharanpreet Lall | Yang Liu | Stefanie Friedrich | Mazlina Ismail | Alex Hoyle | Adnan Ali | Aine Haran | Anna Wingate | Leila Zakka | Daniel Wetterskog | Claire Amos | Nafisah Atako | Victoria Wang | Hannah Rush | Robert Jones | Hing Leung | William Cross | Silke Gillessen | Chris Parker | Simon Chowdhury | Tamara Lotan | Teresa Marafioti | Alfonso Urbanucci | Edward Schaeffer | Daniel Spratt | David Waugh | Thomas Powles | Daniel Berney | Matthew Sydes | Mahesh Parmar | Anis Hamid | Felix Feng | Christopher Sweeney | Elai Davicioni | Noel Clarke | Nicholas James | Louise Brown
Research square | 2023

Metastatic and high-risk localized prostate cancer respond to hormone therapy but outcomes vary. Following a pre-specified statistical plan, we used Cox models adjusted for clinical variables to test associations with survival of multi-gene expression-based classifiers from 781 patients randomized to androgen deprivation with or without abiraterone in the STAMPEDE trial. Decipher score was strongly prognostic (p<2x10 -5 ) and identified clinically-relevant differences in absolute benefit, especially for localized cancers. In metastatic disease, classifiers of proliferation, PTEN or TP53 loss and treatment-persistent cells were prognostic. In localized disease, androgen receptor activity was protective whilst interferon signaling (that strongly associated with tumor lymphocyte infiltration) was detrimental. Post-Operative Radiation-Therapy Outcomes Score was prognostic in localized but not metastatic disease (interaction p=0.0001) suggesting the impact of tumor biology on clinical outcome is context-dependent on metastatic state. Transcriptome-wide testing has clinical utility for advanced prostate cancer and identified worse outcomes for localized cancers with tumor-promoting inflammation.

Pubmed ID: 36798177

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This is a list of tools and resources that we have found mentioned in this publication.


DECIPHER (tool)

RRID:SCR_006552

Interactive database which incorporates a suite of tools designed to aid the interpretation of submicroscopic chromosomal imbalance. Used to enhance clinical diagnosis by retrieving information from bioinformatics resources relevant to the imbalance found in the patient. Contributing to the DECIPHER database is a Consortium, comprising an international community of academic departments of clinical genetics. Each center maintains control of its own patient data (which are password protected within the center''''s own DECIPHER project) until patient consent is given to allow anonymous genomic and phenotypic data to become freely viewable within Ensembl and other genome browsers. Once data are shared, consortium members are able to gain access to the patient report and contact each other to discuss patients of mutual interest, thus facilitating the delineation of new microdeletion and microduplication syndromes.

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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biomaRt (tool)

RRID:SCR_019214

Software package that integrates BioMart data resources with data analysis software in Bioconductor. Can annotate range of gene or gene product identifiers including Entrez Gene and Affymetrix probe identifiers with information such as gene symbol, chromosomal coordinates, Gene Ontology and OMIM annotation. Enables retrieval of genomic sequences and single nucleotide polymorphism information, which can be used in data analysis.

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