Table 3.
Association Between Biomarker Levels, Clinical Covariates and Outcome for HCC Patients
| Variables | Progression-Free Survival | Overall Survival | |||||
|---|---|---|---|---|---|---|---|
| Univariate Analysis | HR | 95% CI | P-value | HR | 95% CI | P-value | |
| Age | Continuous | 1.01 | 0.99–1.03 | 0.332 | 1.01 | 0.99–1.04 | 0.280 |
| Gender (male) | Male vs female | 0.78 | 0.36–1.71 | 0.533 | 1.04 | 0.41–2.65 | 0.932 |
| BMI | Continuous | 1.01 | 0.97–1.05 | 0.672 | 0.99 | 0.94–1.04 | 0.634 |
| Child-Pugh score | B/C vs A | 2.39 | 1.37–4.19 | 0.002 | 5.06 | 2.58–9.93 | <0.0001 |
| Size of largest lesion | Continuous | 1.08 | 1.02–1.14 | 0.007 | 1.14 | 1.07–1.22 | 0.0001 |
| Number of lesions | Continuous | 1.18 | 1.08–1.29 | 0.0003 | 1.41 | 1.22–1.63 | <0.0001 |
| Portal vein invasion | Yes vs no | 2.57 | 1.25–5.11 | 0.010 | 3.53 | 1.52–8.21 | 0.003 |
| PC3X | Continuous | 1.02 | 1.01–1.04 | 0.007 | 1.03 | 1.00–1.06 | 0.054 |
| High (23.9–122.8 ng/mL, Q4) vs low (5.2–23.5 ng/mL, Q1-Q3) | 1.80 | 1.05–3.08 | 0.032 | 2.12 | 1.10–4.05 | 0.024 | |
| PRO-C3 | Continuous | 1.01 | 1.00–1.03 | 0.020 | 1.01 | 0.99–1.03 | 0.052 |
| High (52.3–113.3 ng/mL, Q4) vs low (5.3–51.8 ng/mL, Q1-Q3) | 1.19 | 0.99–1.42 | 0.059 | 1.12 | 0.89–1.41 | 0.324 | |
| AFP | Continuous | 1.00 | 1.00–1.00 | 0.171 | 1.00 | 1.00–1.00 | 0.030 |
| High vs low (≥20 vs <20 IU/mL) | 1.70 | 1.05–2.76 | 0.031 | 2.55 | 1.38–4.69 | 0.003 | |
| PC3X and AFP | High PC3X and high AFP vs low PC3X and/or low AFP | 2.66 | 1.37–5.18 | 0.004 | 5.86 | 2.57–13.37 | <0.0001 |
| Multivariate Analysis | HR | 95% CI | P-value | HR | 95% CI | P-value | |
| Adjusted for age, gender and BMI | |||||||
| PC3X | High vs low (Q4 vs Q1-Q3) | 1.88 | 1.07–3.31 | 0.028 | 2.54 | 1.27–5.08 | 0.008 |
| AFP | High vs low (≥20 vs <20 IU/mL) | 1.64 | 0.99–2.73 | 0.054 | 2.50 | 1.31–4.75 | 0.005 |
| PC3X and AFP | High PC3X and high AFP vs low PC3X and/or low AFP | 2.81 | 1.38–5.74 | 0.004 | 6.35 | 2.66–15.15 | <0.0001 |
| Adjusted for Child-Pugh score | |||||||
| PC3X | High vs low (Q4 vs Q1-Q3) | 1.53 | 0.87–2.67 | 0.140 | 2.23 | 1.12–4.47 | 0.023 |
| AFP | High vs low (≥20 vs <20 IU/mL) | 1.96 | 1.17–3.29 | 0.011 | 4.53 | 2.24–9.19 | <0.0001 |
| PC3X and AFP | High PC3X and high AFP vs low PC3X and/or low AFP | 2.68 | 1.36–5.28 | 0.004 | 8.17 | 3.31–20.13 | <0.0001 |
| Adjusted for size of largest lesion, number of lesions and presence of portal vein invasion | |||||||
| PC3X | High vs low (Q4 vs Q1-Q3) | 1.43 | 0.79–2.59 | 0.241 | 1.47 | 0.69–3.13 | 0.317 |
| AFP | High vs low (≥20 vs <20 IU/mL) | 1.65 | 0.98–2.76 | 0.059 | 2.26 | 1.12–4.56 | 0.023 |
| PC3X and AFP | High PC3X and high AFP vs low PC3X and/or low AFP | 2.01 | 0.99–4.07 | 0.053 | 4.40 | 1.77–10.89 | 0.001 |
| PC3X adjusted for AFP | High vs low (Q4 vs Q1-Q3) | 1.74 | 1.01–2.98 | 0.045 | 2.21 | 1.15–4.27 | 0.018 |
Notes: Hazard ratios were calculated by univariate and multivariate Cox proportional-hazard analysis; By univariate analysis, PC3X and PRO-C3 were analyzed on both a continuous scale and divided into quartiles with the lower levels (Q1-Q3) used as a reference to calculate the HR for patients in the upper quartile (Q4); The covariates were analyzed on a continuous scale, and Child-Pugh score and AFP were furthermore analyzed on a binominal scale; By multivariable analysis, PC3X and AFP were adjusted as indicated in the text.
Abbreviations: AFP, alpha-fetoprotein; BMI, body mass index; HR, hazard ratio.