Laurent Gole1, Joe Yeong1,2,3, Jeffrey Chun Tatt Lim1,2, Kok Haur Ong1, Hao Han1,4, Aye Aye Thike2, Yong Cheng Poh5, Sidney Yee5, Jabed Iqbal2, Wanjin Hong6, Bernett Lee7, Weimiao Yu8, Puay Hoon Tan9. 1. Institute of Molecule and Cell Biology, A*STAR, 61 Biopolis Drive, Proteos, Building, Singapore, 138673, Singapore. 2. Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore. 3. Singapore Immunology Network, A*STAR, 8A Biomedical Grove, Immunos Building, Biopolis, Singapore, 138648, Singapore. 4. Department of Pathology, National University Hospital, Singapore, Singapore. 5. Diagnostic Development Hub (DxD), A*STAR, Singapore, Singapore. 6. Institute of Molecule and Cell Biology, A*STAR, 61 Biopolis Drive, Proteos, Building, Singapore, 138673, Singapore. mcbhwj@imcb.a-star.edu.sg. 7. Singapore Immunology Network, A*STAR, 8A Biomedical Grove, Immunos Building, Biopolis, Singapore, 138648, Singapore. bernett_lee@immunol.a-star.edu.sg. 8. Institute of Molecule and Cell Biology, A*STAR, 61 Biopolis Drive, Proteos, Building, Singapore, 138673, Singapore. wmyu@imcb.a-star.edu.sg. 9. Division of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 7, Diagnostics Tower, Singapore, 169856, Singapore. tan.puay.hoon@singhealth.com.sg.
Abstract
BACKGROUND: Stromal and collagen biology has a significant impact on tumorigenesis and metastasis. Collagen is a major structural extracellular matrix component in breast cancer, but its role in cancer progression is the subject of historical debate. Collagen may represent a protective layer that prevents cancer cell migration, while increased stromal collagen has been demonstrated to facilitate breast cancer metastasis. METHODS: Stromal remodeling is characterized by collagen fiber restructuring and realignment in stromal and tumoral areas. The patients in our study were diagnosed with triple-negative breast cancer in Singapore General Hospital from 2003 to 2015. We designed novel image processing and quantification pipelines to profile collagen structures using numerical imaging parameters. Our solution differentiated the collagen into two distinct modes: aggregated thick collagen (ATC) and dispersed thin collagen (DTC). RESULTS: Extracted parameters were significantly associated with bigger tumor size and DCIS association. Of numerical parameters, ATC collagen fiber density (CFD) and DTC collagen fiber length (CFL) were of significant prognostic value for disease-free survival and overall survival for the TNBC patient cohort. Using these two parameters, we built a predictive model to stratify the patients into four groups. CONCLUSIONS: Our study provides a novel insight for the quantitation of collagen in the tumor microenvironment and will help predict clinical outcomes for TNBC patients. The identified collagen parameters, ATC CFD and DTC CFL, represent a new direction for clinical prognosis and precision medicine. We also compared our result with benign samples and DICS samples to get novel insight about the TNBC heterogeneity. The improved understanding of collagen compartment of TNBC may provide insights into novel targets for better patient stratification and treatment.
BACKGROUND: Stromal and collagen biology has a significant impact on tumorigenesis and metastasis. Collagen is a major structural extracellular matrix component in breast cancer, but its role in cancer progression is the subject of historical debate. Collagen may represent a protective layer that prevents cancer cell migration, while increased stromal collagen has been demonstrated to facilitate breast cancer metastasis. METHODS: Stromal remodeling is characterized by collagen fiber restructuring and realignment in stromal and tumoral areas. The patients in our study were diagnosed with triple-negative breast cancer in Singapore General Hospital from 2003 to 2015. We designed novel image processing and quantification pipelines to profile collagen structures using numerical imaging parameters. Our solution differentiated the collagen into two distinct modes: aggregated thick collagen (ATC) and dispersed thin collagen (DTC). RESULTS: Extracted parameters were significantly associated with bigger tumor size and DCIS association. Of numerical parameters, ATC collagen fiber density (CFD) and DTC collagen fiber length (CFL) were of significant prognostic value for disease-free survival and overall survival for the TNBCpatient cohort. Using these two parameters, we built a predictive model to stratify the patients into four groups. CONCLUSIONS: Our study provides a novel insight for the quantitation of collagen in the tumor microenvironment and will help predict clinical outcomes for TNBCpatients. The identified collagen parameters, ATC CFD and DTC CFL, represent a new direction for clinical prognosis and precision medicine. We also compared our result with benign samples and DICS samples to get novel insight about the TNBC heterogeneity. The improved understanding of collagen compartment of TNBC may provide insights into novel targets for better patient stratification and treatment.
Entities:
Keywords:
Collagen profile; Quantitative imaging; Second harmonic generation microscopy; Stroma; Triple-negative breast cancers
Authors: Ana P V Garcia; Luana A Reis; Fernanda C Nunes; Francis G J Longford; Jeremy G Frey; Ana M de Paula; Geovanni D Cassali Journal: Sci Rep Date: 2021-03-11 Impact factor: 4.379