PacRim7 7th PacRim Meeting Poster Presentations (1) (52 abstracts)
LobSig, a prognostic signature for ILC
Amy E McCart Reed 1 , Samir Lal 1 , Katia Nones 2 , Jamie R Kutasovic 1 , Craig P Coorey 1 , Priyakshi Kalita de Croft 1 , Andrew Dalley 1 , Luyu Kuo 1 , Leesa Wockner 2 , Alan Robertson 3 , Kaltin Ferguson 1 , Colleen Niland 1 , Mythily Sachchithananthan 1, , Ana Cristina Vargas 1 , Gregory Miller 1 , Debra Black 1 , Julie Johnson 1 , Lynne E Reid 1 , Renique Males 1 , Irma Gresshoff 1 , Alan Porter 4 , Elizabeth Evans 4 , Jodi M Saunus 1 , Fares Al-Ejeh 2 , John V Pearson 2 , Georgia Chenevix-Trench 2 , Lachlan Coin 3 , Nicola Waddell 2 , Sunil R Lakhani 1, & Peter T Simpson 1
1UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, 4029, QLD, Australia; 2QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia; 3Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia; 4Wesley Breast Clinic, Auchenflower, Queensland 4066, Australia; 5Pathology Queensland, The Royal Brisbane & Women’s Hospital, Herston, 4029, QLD, Australia; 6Australian Breast Cancer Tissue Bank, Westmead, 2145, NSW, Australia.
Invasive lobular carcinoma (ILC) is the most common special type of breast cancer, and is characterized by functional loss of E-cadherin, resulting in cellular adhesion defects. ILC typically present as estrogen receptor positive, grade 2 breast cancers, with a good short-term prognosis. Several large-scale molecular profiling studies have now dissected the unique genomics of ILC. We have undertaken an integrative analysis of gene expression and DNA copy number to identify novel drivers, and prognostic biomarkers, using in-house (n=25), METABRIC (n=125) and TCGA (n=145) samples. Using in silico integrative analyses a 194-gene set was derived that is highly prognostic in ILC (P=1.20 × 10−5) – we named this metagene ‘LobSig’. Network analysis identified few candidate pathways, though gene sets related to proliferation were identified, and a LobSig-high phenotype was associated with the TCGA proliferative group (c2 P<8.86×10−4). Within a 10-year follow-up period, LobSig outperformed the Nottingham Prognostic Index, PAM50 risk-of-recurrence (Prosigna), OncotypeDx, and MapQuantDx (Genomic Grade Index) in a stepwise, multivariate Cox proportional hazards model, particularly in grade 2 cases (χ2P=9.0×10−6) which present most frequently and are difficult to prognosticate clinically. Importantly, LobSig status predicted outcome with 96.6% accuracy amongst cases classified as ‘moderate risk’ according to Nottingham Prognostic Index in the METABRIC cohort. LobSig is a clinically relevant prognostic signature which warrants future development.
Article tools
My recent searches
My recently viewed abstracts
Authors
Oncology Abstracts
ISSN 2631-4657 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more