Prognostic value of preoperative serum bilirubin levels in ovarian cancer

Abstract

Bilirubin is a promising prognostic factor for non-liver disease-related deaths in various cancers. We investigated the association between preoperative serum bilirubin levels and oncological outcomes in patients with ovarian cancer. We retrospectively analyzed the clinical data of 282 patients with epithelial ovarian carcinoma (EOC), and grouped them according to optimal threshold values of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBL) measured by receiver operating characteristic curve analysis. Univariate and multivariate Cox proportional hazards regression analyses were used to evaluate various parameters that might affect overall survival (OS) and progression-free survival (PFS) in patients with EOC. The optimal cutoff values for TBIL, DBIL, and IBIL levels were 9.65 µmol/L, 2.95 µmol/L, and 6.75 µmol/L, respectively. Increased TBIL, DBIL, and IBIL levels correlated with the serum carbohydrate antigen (CA)-125 levels, International Federation of Gynecology and Obstetrics stage, and pathological differentiation (all P<0.05). Univariate analysis revealed longer OS and PFS in patients with high TBIL (≥9.65 µmol/L) and IBIL (≥6.75 µmol/L) levels (P<0.05). Multivariate analysis showed that patients with high IBIL levels (≥6.75 µmol/L) had significantly longer OS and PFS than those with low IBIL levels (<6.75 µmol/L) [hazard ratio (HR) = 0.333, 95% confidence interval (CI): 0.123~0.904, P<0.05; HR = 1.814, 95% CI: 1.169~2.816, P<0.05]. Therefore, IBIL is a potential independent prognostic factor for OS and PFS in patients with EOC. The higher the IBL level, the better the prognosis of patients with EOC.

Keywords: Bilirubin; epithelial ovarian carcinoma; overall survival; prognosis; progression-free survival.

Figure 1

ROC curve to build a predictive model for risk of ovarian cancer. TBIL, IBL, DBIL, preoperative CA125 level, tumor size and age were selected according to the ROC curve to obtain the optimal interception point (9.65 µmol/L, 6.75 µmol/L, 2.95 µmol/L, 124 U/mL, 9 cm and 65 years old) for the analysis of influencing factors of OS.

Figure 2

Univariate analysis of overall survival in EOC patients. Kaplan-Meier survival curves showing the effects of TBIL and IBL for OS and PFS. TBIL and IBL survival curves were statistically significant for OS (P-value = 0.001, chi-square = 12.020; P-value = 0.002, chi-squared = 9.384) and for PFS (P-value = 0.000, chi-squared = 15.990). P-value = 0.001, chi-squared = 11.356).