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Table 1 Collagen features in breast cancer research

From: The association between tumor-stromal collagen features and the clinical outcomes of patients with breast cancer: a systematic review

Feature Category

Features

Definition

Measurement Methodologies

Quantity/Density

Total collagen density/volume

Overall collagen content in tissue, reflecting synthesis, deposition, or degradation.

SHG microscopy (collagen fiber volume, pixel ratio), Masson’s trichrome/Sirius Red staining (collagen area percentage), IHC/real-time PCR (COL1A1 expression).

Collagen intensity

Signal strength of collagen in stained or imaged samples.

Sirius Red staining (light microscopy), SHG microscopy (signal intensity).

Collagen Morphology

Fiber curvature/straightness

Degree of bending in fibers (curvature) or linearity (straightness).

SHG microscopy + CT-FIRE/CurveAlign (fiber tracing), ANN-based segmentation (length/width ratios).

Fiber width/thickness

Diameter or thickness of individual collagen fibers.

SHG/PLM imaging + CT-FIRE, CurveAlign.

Fiber length

End-to-end or contour length of collagen fibers.

SHG microscopy + CT-FIRE, CurveAlign, ANN segmentation.

Collagen Organization

Fiber alignment/anisotropy

Directional uniformity of fibers (0 = random, 1 = aligned).

SHG microscopy + CurveAlign (anisotropy coefficients), PLM (birefringence analysis).

Collagen orientation index

Quantifies alignment (0 = random, 1 = linear).

FFT analysis + ellipse fitting (aspect ratio).

GLCM parameters

Spatial relationships between pixels (e.g., correlation, energy).

Texture analysis of SHG/Sirius Red images (GLCM matrices).

Ratio parameter (PSHG)

Proportion of fibrils conforming to polarized SHG model.

Polarization-dependent SHG (PSHG) + FFT analysis.

Collagen Microstructure

F/B SHG ratio

Forward-to-backward SHG signal ratio; reflects fibril diameter/packing.

SHG microscopy (emission direction analysis).

Perpendicular Relative to Tumor Boundary

TACS-3 signature

Straightened, aligned collagen fibers perpendicular to tumor boundary.

SHG microscopy + computational scoring (fiber angle, alignment).

Prognostic Indices

TACS scores (1–3, 1–8)

Composite scores of collagen signatures (e.g., TACS-3 = perpendicular fibers).

SHG imaging + ridge/LASSO regression (weighted collagen patterns).

TCMF score

Microscopic collagen features (e.g., fiber length, texture).

Multiphoton microscopy + LASSO regression.

IGNN score

Spatial heterogeneity of TACS patterns via graph neural networks.

SHG imaging + graph neural networks (spatial biomarker interactions).

Collagen Prognostic Index

Combines directionality, density, and dispersion scores.

Picrosirius Red staining + scoring system.

  1. Abbreviations: COL1A1 Collagen Type I Alpha 1, F/B Forward-to-Backward ratio, FFT Fast Fourier Transform, GLCM Gray-level co-occurrence matrix, IHC Immunohistochemistry, IGNN Intratumor graph neural network, LASSO least absolute shrinkage and selection operator, PSHG Polarization-dependent Second Harmonic Generation, TACSs Tumor-associated collagen signatures, TCMFs TACS corresponding microscopic features, SHG Second Harmonic Generation, PLM Polarized Light Microscopy
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Breast Cancer Research

ISSN: 1465-542X

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