Fig. 1: Workflow of CoDA feature extraction and prognostic analysis in colon cancer. | npj Precision Oncology

Fig. 1: Workflow of CoDA feature extraction and prognostic analysis in colon cancer.

From: Collagen disorder architecture features are associated with clinical, molecular, genetic factors and survival outcomes in colon cancer

Fig. 1

(1) CoDA FEATURE CALCULATION METHDOLOGY: (A) Whole Slide Image (WSI) from colon cancer patient (B) Tumor mask+HistoQC mask overlaid on WSI (C) Tiling of the WSI from the subtracted masked region (D) Example tiles (E) Collagen fibers within the stroma region of exmaple tile detected by a derivative-of-Gaussian (DtG) based model (F) Collagen fiber fragmentation (G) Collagen fiber bundling (H) Collagen fiber rigidity (I) Collagen fiber anisotropy. As the anisotropy values increase, the colormap transitions to green color at the highest end of the scale (corresponding to well aligned or anisotropic orientation). J Collagen fiber density. Hotter colors such as red and yellow represent higher density values while cooler colors such as blue and green represent lower density values in the density scale. K Cropped portion of Collagen fiber fragmentation (L) Cropped portion of Collagen fiber bundling (M) Cropped portion of Collagen fiber rigidity (N) Representation of tumor region tiles with example CoDA feature: Density, restitched back into their corresponding positions within the WSI. (2) STATISTICAL ANALYSIS: (A) Violin plots showing distribution across KRAS,BRAF and NRAS mutational variables for the individual CoDA features i.e., CF Fragmentation, CF Bundling, CF Anisotropy, CF Density and CF Rigidity. Significant differences between the groups (example: KRAS wild type vs KRAS mutated) were calculated by Mann–Whitney U test with Bonferroni corrected p values (*p) reported. Similar tests were done for clinical (Overall Stage, T Stage, N Stage and M Stage) and molecular variables (CMS1-4). Example Kaplan Meier plots showing risk stratified high and low risk groups, as derived using CoDA features using LASSO Cox proportional Hazards Model, for KRAS wild type for (B) Overall Survival (OS) and (C) Disease Free Survival (DFS). Risk stratification was done for other mutational variables (KRAS mutated, BRAF wild type and mutated and NRAS wild type and mutated) alongwith clinical and molecular variables. D To show CoDA as independent prognostic features, Multivariable Cox Proportional Hazards Analysis was done for OS and DFS for clinical, molecular and genetic variables alongwith variables like age, gender and race. Hazard ratios (HR) with corresponding 95% confidence intervals (CI) are presented.

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