Table 2

Univariate and multivariate Cox regression analysis of the association of patient factors and ECM biomarkers with progression-free survival (PFS)

Factor	Test variable	Events/total cases	Univariate	P value	Events/Total cases	Multivariate Adjusted for LDH	P value
Factor	Test variable	Events/total cases	HR (95% CI)	P value	Events/Total cases	HR (95% CI)	P value
Gender	Male vs female	40/62 vs 26/44	1.14 (0.69 to 1.86)	0.611
Age	Continuous (year)	66/106	1.00 (0.99 to 1.02)	0.744
WHO	>1 vs 0	27/37 vs 39/69	1.60 (0.98 to 2.62)	0.061
Brain metastasis	Present vs absent	12/18 vs 33/47	1.00 (0.52 to 1.94)	0.997
LDH	Continuous (U/L)	66/106	1.00 (1.00 to 1.00)	0.014*
PRO-C3	Continuous (ng/mL)	66/106	1.02 (1.00 to 1.04)	0.031*
	4.0–12.5 ng/mL, Q1-–Q3	45/79	1.00	–	45/79
	12.6–84.7 ng/mL, Q4	21/27	1.96 (1.17 to 3.30)	0.011*	21/27	1.81 (1.06 to 3.10)	0.030*
PC3X	Continuous (ng/mL)	66/10644/79	1.04 (1.00 to 1.07)	0.046*
	1.2–7.6 ng/mL, Q1-–Q3		1.00	–	44/79
	7.6–30.2 ng/mL, Q4	22/27	2.05 (1.23 to 3.43)	0.006**	22/27	1.86 (1.09 to 3.18)	0.023*
C4G	Continuous (ng/mL)	65/105	1.01 (1.00 to 1.02)	0.019*
	7.8–27.3 ng/mL, Q1-–Q3	44/79	1.00	–	44/79
	27.4–125.7 ng/mL, Q4	21/26	1.93 (1.15 to 3.26)	0.014*	21/26	1.91 (1.13 to 3.23)	0.016*
C3M	Continuous (ng/mL)	66/106	1.04 (1.00 to 1.09)	0.038*
	8.2–19.5 ng/mL, Q1–Q3	45/79	1.00	–	45/79
	19.6–36.0 ng/mL, Q4	21/27	1.75 (1.04 to 2.93)	0.036*	21/27	1.67 (0.99 to 2.82)	0.054
C4M	Continuous (ng/mL)	66/106	1.01 (1.00 to 1.03)	0.158
	8.8–38.0 ng/mL, Q1–Q3	47/79	1.00	–	47/79
	38.8–87.1 ng/mL, Q4	19/27	1.29 (0.76 to 2.20)	0.349	19/27	1.19 (0.69 to 2.04)	0.532
VICM	Continuous (ng/mL)	66/106	1.01 (1.00 to 1.02)	0.121
	1.0–23.4 ng/mL, Q1–Q3	48/79	1.00	–	48/79
	23.7–132.3 ng/mL, Q4	18/27	1.16 (0.67 to 1.99)	0.602	18/27	1.27 (0.73 to 2.20)	0.401
C3M/PRO-C3	>1 vs <1	51/88 vs 15/18	0.51 (0.29 to 0.91)	0.023*	51/88 vs 15/18	0.59 (0.32 to 1.11)	0.102

HR were calculated by univariate and multivariate cox regression analysis. By the multivariate analysis, the individual biomarkers were adjusted for LDH. Significance is marked with stars.
C4G, granzyme B-degraded type IV collagen; C3M, C4M, matrix metalloprotease (MMP)-degraded type III and IV collagen; ECM, extracellular matrix; LDH, lactate dehydrogenase; PC3X, cross-linked N-terminal pro-peptide of type III collagen; PRO-C3, N-terminal pro-peptide of type III collagen; VICM, citrullinated and MMP-degraded vimentin; WHO, WHO performance score.