Table 2.
Univariate and multivariate analysis of CD73 and clinicopathological variables with outcomes.
| Time to recurrence | Disease specific survival | |||
| |
HR (95% CI) |
P value |
HR (95% CI) |
P value |
| Total cohort (N = 215) | ||||
| Univariate Analysis | ||||
| Age at hepatectomy (≤65 vs >65 years) | 0.94 (0.68 - 1.31) | 0.718 | 1.38 (0.92 - 2.07) | 0.115 |
| Gender (male vs female) | 1.04 (0.74 - 1.47) | 0.818 | 1.25 (0.83 - 1.88) | 0.292 |
| Timing of metastasis (synchronous vs metachronous) | 0.82 (0.59 - 1.14) | 0.239 | 0.81 (0.54 - 1.21) | 0.300 |
| Number of metastases (single vs multiple) | 1.72 (1.23 - 2.41) | 0.002 | 1.34 (0.88 - 2.03) | 0.176 |
| Diameter of largest metastasis (≤5 vs >5 cm | 1.41 (0.90 - 2.20) | 0.130 | 1.25 (0.69 - 2.24) | 0.464 |
| Disease-free interval <12 months (no vs yes) | 1.79 (1.23 - 2.61) | 0.002 | 1.87 (1.14 - 3.06) | 0.013 |
| CEA level (≤200 vs >200 ng/mL) | 5.32 (2.13 - 13.29) | <0.001 | 3.98 (1.73 - 9.14) | 0.001 |
| Liver resection margin (negative vs positive for cancer cells) | 1.43 (0.81 - 2.53) | 0.221 | 2.36 (1.31 - 4.25) | 0.004 |
| Tertiary lymphoid structure (no vs yes) | 0.86 (0.50 - 1.50) | 0.603 | 0.35 (0.15 - 0.81) | 0.014 |
| Necrosis (≤ 25 vs > 25 %) | 0.97 (0.64 - 1.46) | 0.876 | 1.55 (0.95 - 2.52) | 0.077 |
| Primary tumor (left vs right) | 0.91 (0.63 - 1.33) | 0.637 | 1.16 (0.73 - 1.83) | 0.530 |
| pT category (T1-T2-T3 vs T4) | 2.12 (1.39 - 3.23) | 0.001 | 2.17 (1.36 - 3.48) | 0.001 |
| pN category (N0 vs N+) | 1.43 (1.01 - 2.02) | 0.044 | 1.60 (1.02 - 2.52) | 0.041 |
| Preop chemotherapy (no vs yes) | 1.51 (0.98 - 2.30) | 0.059 | 1.78 (1.01 - 3.13) | 0.047 |
| tCD73 (low vs high) | 1.70 (1.22 - 2.36) | 0.002 | 1.92 (1.28 - 2.86) | 0.002 |
| sCD73 (low vs high) | 1.00 (0.89 - 1.13) | 0.985 | 1.08 (0.94 - 1.23) | 0.270 |
| Multivariate Analysis | ||||
| CEA level (≤200 vs >200 ng/mL) | 4.83 (1.90 - 12.27) | 0.001 | 3.83 (1.48 - 9.89) | 0.006 |
| Disease-free interval <12 months (no vs yes) | 1.73 (1.17 - 2.56) | 0.006 | 2.05 (1.22 - 3.44) | 0.007 |
| Liver resection margin (negative vs positive for cancer cells) | - | - | 2.39 (1.28 - 4.49) | 0.007 |
| Tertiary lymphoid structure (no vs yes) | - | - | 0.34 (0.15 - 0.79) | 0.013 |
| pT category (T1-T2-T3 vs T4) | 1.99 (1.30 - 3.06) | 0.002 | 2.35 (1.45 - 3.80) | 0.001 |
| tCD73 (low vs high) |
1.55 (1.09 - 2.21) |
0.014 |
1.94 (1.26 - 2.98) |
0.003 |
| Preoperative chemotherapy (n = 169) | ||||
| Univariate Analysis | ||||
| Age at hepatectomy (≤65 vs >65 years) | 0.97 (0.67 - 1.39) | 0.852 | 1.46 (0.94 - 2.25) | 0.094 |
| Gender (male vs female) | 1.03 (0.70 - 1.50) | 0.882 | 1.30 (0.83 - 2.03) | 0.251 |
| Timing of metastasis (synchronous vs metachronous) | 0.96 (0.67 - 1.37) | 0.817 | 0.93 (0.61 - 1.43) | 0.748 |
| Number of metastases (single vs multiple) | 1.52 (1.03 - 2.23) | 0.035 | 1.30 (0.80 - 2.09) | 0.287 |
| Diameter of largest metastasis (≤5 vs >5 cm | 1.53 (0.93 - 2.53) | 0.097 | 1.73 (0.91 - 3.27) | 0.095 |
| Disease-free interval <12 months (no vs yes) | 1.42 (0.90 - 2.24) | 0.134 | 1.21 (0.68 - 2.14) | 0.525 |
| CEA level (≤200 vs >200 ng/mL) | 3.81 (1.19 - 12.19) | 0.024 | 5.42 (1.94 - 15.15) | 0.001 |
| Liver resection margin (negative vs positive for cancer cells) | 1.78 (0.97 - 3.24) | 0.061 | 2.54 (1.37 - 4.71) | 0.003 |
| Tertiary lymphoid structure (no vs yes) | 0.82 (0.43 - 1.57) | 0.548 | 0.47 (0.20 - 1.08) | 0.075 |
| Necrosis (≤ 25 vs > 25 %) | 0.99 (0.64 - 1.56) | 0.980 | 1.56 (0.93 - 2.61) | 0.091 |
| Primary tumor (left vs right) | 0.80 (0.54 - 1.21) | 0.291 | 0.90 (0.55 - 1.47) | 0.662 |
| pT category (T1-T2-T3 vs T4) | 1.74 (1.10 - 2.75) | 0.018 | 2.01 (1.22 - 3.32) | 0.006 |
| pN category (N0 vs N+) | 1.19 (0.81 - 1.75) | 0.368 | 1.48 (0.90 - 2.41) | 0.120 |
| Oxaliplatin-based chemotherapy pre-op (no vs yes) | 1.04 (0.60 - 1.79) | 0.894 | 1.53 (0.74 - 3.18) | 0.253 |
| Bevacuzimab pre-op (no vs yes) | 1.21 (0.77 - 1.91) | 0.404 | 1.43 (0.81 - 2.52) | 0.217 |
| Tumor Regression Grade (1-2 vs 3-4-5) | 1.64 (0.98 - 2.74) | 0.061 | 1.09 (0.60 - 1.97) | 0.780 |
| tCD73 (low vs high) | 1.96 (1.36 - 2.82) | <0.001 | 1.78 (1.15 - 2.75) | 0.009 |
| sCD73 (low vs high) | 0.99 (0.86 - 1.13) | 0.844 | 1.14 (1.00 - 1.30) | 0.053 |
| Multivariate Analysis | ||||
| CEA level (≤200 vs >200 ng/mL) | - | - | 5.48 (1.65 - 18.19) | 0.005 |
| pT category (T1-T2-T3 vs T4) | - | - | 2.15 (1.29 - 3.58) | 0.003 |
| Liver resection margin (negative vs positive for cancer cells) | - | - | 2.62 (1.36 - 5.03) | 0.004 |
| tCD73 (low vs high) | 2.00 (1.37 - 2.94) | <0.001 | 1.72 (1.08 - 2.74) | 0.022 |
Abbreviations: HR, Hazard ratio; CI, Confidence interval; tCD73, tumoral CD73 expression in CRLM ; sCD73, soluble CD73 measured in serum; CEA, Carcinoembryoinic Antigen; T, Tumor; N, Node.