Table 1 Association of CoDA features with clinical, molecular, and genetic subgroups are presented

Variable type	Variables	CoDA features	p values	Bonferroni-corrected p-values (*p)
CLINICAL	OVERALL STAGE	CF fragmentation	0.001	0.004
		CF bundling	0.02	0.10
		CF anisotropy	0.004	0.01
		CF density	0.02	0.12
		CF rigidity	0.01	0.04
	T STAGE	CF fragmentation	0.01	0.07
		CF bundling	0.01	0.05
		CF anisotropy	0.007	0.03
		CF density	0.005	0.02
		CF rigidity	0.009	0.04
	N STAGE	CF fragmentation	0.008	0.04
		CF bundling	0.001	0.007
		CF anisotropy	0.001	0.003
		CF density	0.006	0.03
		CF rigidity	0.007	0.03
	M STAGE	CF fragmentation	0.006	0.03
		CF bundling	0.004	0.02
		CF anisotropy	0.01	0.05
		CF density	0.02	0.13
		CF rigidity	0.01	0.09
MOLECULAR	CMS1	CF fragmentation	0.001	0.006
		CF bundling	0.01	0.05
		CF anisotropy	0.001	0.007
		CF density	0.01	0.09
		CF rigidity	0.02	0.13
	CMS2	CF fragmentation	0.02	0.13
		CF bundling	0.007	0.03
		CF anisotropy	0.01	0.05
		CF density	0.01	0.07
		CF rigidity	0.02	0.11
	CMS3	CF fragmentation	0.02	0.10
		CF bundling	0.006	0.02
		CF anisotropy	0.02	0.12
		CF density	0.009	0.04
		CF rigidity	0.009	0.04
	CMS4	CF fragmentation	0.01	0.05
		CF bundling	0.02	0.12
		CF anisotropy	0.009	0.04
		CF density	0.01	0.05
		CF rigidity	0.02	0.12
GENETIC	KRAS	CF fragmentation	0.006	0.02
		CF bundling	0.001	0.007
		CF anisotropy	0.01	0.07
		CF density	0.002	0.01
		CF rigidity	0.003	0.01
	BRAF	CF fragmentation	0.03	0.15
		CF bundling	0.005	0.02
		CF anisotropy	0.001	0.04
		CF density	0.007	0.03
		CF rigidity	0.00	0.002
	NRAS	CF fragmentation	1.00	1.00
		CF bundling	0.01	0.07
		CF anisotropy	1.00	1.00
		CF density	0.03	0.15
		CF rigidity	0.008	0.04

The Mann–Whitney U test was used to assess differences in CoDA features: CF fragmentation, CF bundling, CF anisotropy, CF density, and CF rigidity, across various clinical stages, CMS subtypes, and mutation-defined groups. Bonferroni correction was applied to adjust for multiple comparisons, with a significance threshold of 0.05 for both raw and corrected p-values (denoted as p and *p, respectively). Statistically significant associations for Bonferroni corrected p values are shown in bold. Significant associations were observed across several variables, particularly for N stage, M stage, and CMS3, where all five CoDA features remained significant after correction (*p < 0.05). Similarly, CoDA features were strongly associated with KRAS mutation status, while NRAS mutation showed minimal association except for CF rigidity. These findings highlight that distinct collagen architectural patterns, as captured by CoDA features, are significantly associated with key clinical stages, molecular subtypes, and genetic mutations in CC, reflecting their potential to capture tumor heterogeneity across multiple biological axes.

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