Quantitative stain-free imaging and digital profiling of collagen structure reveal diverse survival of triple negative breast cancer patients.

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 pr...

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Published in:Breast Cancer Research Vol. 22; no. 1; pp. 1 - 14
Main Authors: Gole, Laurent, Yeong, Joe, Lim, Jeffrey Chun Tatt, Ong, Kok Haur, Han, Hao, Thike, Aye Aye, Poh, Yong Cheng, Yee, Sidney, Iqbal, Jabed, Hong, Wanjin, Lee, Bernett, Yu, Weimiao, Tan, Puay Hoon
Format: research Journal Article
Published: BioMed Central 5/6/2020
Online Access:View this record in EBSCOhost
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      dt: 5/6/2020
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        atl: Quantitative stain-free imaging and digital profiling of collagen structure reveal diverse survival of triple negative breast cancer patients.
      aug:
        au:
          Gole, Laurent
          Yeong, Joe
          Lim, Jeffrey Chun Tatt
          Ong, Kok Haur
          Han, Hao
          Thike, Aye Aye
          Poh, Yong Cheng
          Yee, Sidney
          Iqbal, Jabed
          Hong, Wanjin
          Lee, Bernett
          Yu, Weimiao
          Tan, Puay Hoon
        affil: Institute of Molecule and Cell Biology, A*STAR, 61 Biopolis Drive, Proteos, Building, 138673, Singapore, Singapore
      sug:
        subj:
          Microscopy Methods
          Image Processing, Computer Assisted Methods
          Breast Neoplasms Pathology
          Collagen
          Extracellular Space
          Cell Physiology
          Breast Neoplasms Mortality
          Collagen Metabolism
          Prognosis
          Tissue Array Analysis Methods
          Human
          Female
          Survival
          Neoplasm Grading
          Neoplasm Staging
          Extracellular Space Metabolism
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
          Impact of Events Scale
          Questionnaires
          Scales
          Female
      ab: 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.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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