Table 3.
Univariate and multivariate Cox regression analysis of the association of patient factors and ECM biomarkers with overall survival (OS)
| Factor | Test variable | Events/Total cases | Univariate | P value | Events/Total cases | Multivariate Adjusted for LDH |
P value | Events/Total cases | Multivariate Adjusted for ¤ |
P value |
| HR (95% CI) | HR (95% CI) | HR (95% CI) | ||||||||
| Gender | Male vs female | 25/62 vs 15/45 | 1.31 (0.68 to 2.51) | 0.426 | ||||||
| Age | Continuous (years) | 40/107 | 1.01 (0.99 to 1.03) | 0.410 | ||||||
| WHO | >1 vs 0 | 23/38 vs 17/69 vs | 3.10 (1.64 to 5.86) | <0.001*** | ||||||
| Brain metastases | Present vs absent | 9/18 vs 13/48 | 2.39 (1.01 to 5.68) | 0.049* | ||||||
| LDH | Continuous (U/L) | 40/107 | 1.00 (1.00 to 1.00) | <0.0001**** | ||||||
| PRO-C3 | Continuous (ng/mL) | 40/107 | 1.03 (1.01 to 1.05) | 0.004** | ||||||
| 4.0–12.6 ng/mL, Q1–Q3 | 25/80 | 1.00 | – | 25/80 | 14/49 | |||||
| 12.7–84.7 ng/mL, Q4 | 15/27 | 2.41 (1.26 to 4.60) | 0.008** | 15/27 | 2.08 (1.05 to 4.09) | 0.035* | 8/17 | 1.87 (0.71 to 4.90) | 0.202 | |
| PC3X | Continuous (ng/mL) | 40/107 | 1.04 (1.00 to 1.09) | 0.045* | ||||||
| 1.2–7.6 ng/mL, Q1–Q3 | 26/80 | 1.00 | – | 26/80 | 16/50 | |||||
| 7.6–30.2 ng/mL, Q4 | 14/27 | 2.21 (1.14 to 4.28) | 0.019* | 14/27 | 1.78 (0.88 to 3.60) | 0.106 | 6/16 | 1.03 (0.38 to 2.75) | 0.954 | |
| C4G | Continuous (ng/mL) | 39/106 | 1.00 (0.98 to 1.02) | 0.693 | ||||||
| 7.8–27.3 ng/mL, Q1–Q3 | 31/80 | 1.00 | – | 31/80 | 15/46 | |||||
| 27.4–125.7 ng/mL, Q4 | 8/26 | 0.93 (0.42 to 2.04) | 0.856 | 8/26 | 0.95 (0.43 to 2.09) | 0.902 | 6/19 | 1.68 (0.63 to 4.53) | 0.302 | |
| C3M | Continuous (ng/mL) | 40/107 | 1.02 (0.96 to 1.08) | 0.484 | ||||||
| 8.2–19.5 ng/mL, Q1–Q3 | 29/80 | 1.00 | – | 29/80 | 17/49 | |||||
| 19.6–36.0 ng/mL, Q4 | 11/27 | 1.12 (0.54 to 2.30) | 0.760 | 11/27 | 1.10 (0.54 to 2.27) | 0.788 | 5/17 | 0.71 (0.24 to 2.14) | 0.544 | |
| C4M | Continuous (ng/mL) | 40/107 | 1.01 (0.99 to 1.04) | 0.237 | ||||||
| 8.8–38.0 ng/mL, Q1–Q3 | 29/80 | 1.00 | – | 29/80 | 18/51 | |||||
| 38.8–87.1 ng/mL, Q4 | 11/27 | 1.27 (0.63 to 2.56) | 0.507 | 11/27 | 1.14 (0.56 to 2.30) | 0.720 | 4/15 | 0.66 (0.22 to 1.98) | 0.458 | |
| VICM | Continuous (ng/mL) | 40/107 | 1.01 (0.99 to 1.02) | 0.344 | ||||||
| 1.0–23.4 ng/mL, Q1–Q3 | 30/79 | 1.00 | – | 30/79 | 15/48 | |||||
| 23.7–132.3 ng/mL, Q4 | 10/28 | 0.97 (0.47 to 1.98) | 0.926 | 10/28 | 1.14 (0.55 to 2.37) | 0.731 | 7/18 | 1.23 (0.48 to 3.11) | 0.666 | |
| C3M/PRO-C3 | >1 vs <1 | 28/88 vs 12/19 | 0.33 (0.16 to 0.65) | 0.001* | 28/88 vs 12/19 | 0.42 (0.20 to 0.90) | 0.025* | 15/55 vs 7/11 | 0.39 (0.14 to 1.06) | 0.066 |
HR were calculated by univariate and multivariate cox regression analysis. In one multivariate analysis, the individual biomarkers were adjusted for LDH and in the other they were adjusted for LDH, WHO and brain metastases (indicated by ¤). 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.