A nomogram based on pretreatment levels of serum bilirubin and total bile acid levels predicts survival in colorectal cancer patients

Abstract

Background: Serum bilirubin and total bile acid (TBA) levels have been reported to be strongly associated with the risk and prognosis of certain cancers. Here, we aimed to investigate the effects of pretreatment levels of serum bilirubin and bile acids on the prognosis of patients with colorectal cancer (CRC).

Methods: A retrospective cohort of 1474 patients with CRC who underwent surgical resection between January 2015 and December 2017 was included in the study. Survival analysis was used to evaluate the predictive value of pretreatment levels of bilirubin and bile acids. X-Tile software was used to identify optimal cut-off values for total bilirubin (TBIL), direct bilirubin (DBIL) and TBA in terms of overall survival (OS) and disease-free survival (DFS).

Results: DBIL, TBIL, and TBA were validated as significant prognostic factors by univariate Cox regression analysis for both 3-year OS and DFS. Multivariate Cox regression analyses confirmed that high DBIL, TBIL and TBA levels were independent prognostic factors for both OS (HR: 0.435, 95% CI: 0.299-0.637, P < 0.001; HR: 0.436, 95% CI: 0.329-0.578, P < 0.001; HR: 0.206, 95% CI: 0.124-0.341, P < 0.001, respectively) and DFS (HR: 0.583, 95% CI: 0.391-0.871, P = 0.008; HR:0.437,95% CI: 0.292-0.655, P <0.001; HR: 0.634, 95% CI: 0.465-0.865, P = 0.004, respectively). In addition, nomograms for OS and DFS were established according to all significant factors, and the c-indexes were 0.819 (95% CI: 0.806-0.832) and 0.835 (95% CI: 0.822-0.849), respectively.

Conclusions: TBIL, DBIL and TBA levels are independent prognostic factors in colorectal cancer patients. The nomograms based on OS and DFS can be used as a practical model for evaluating the prognosis of CRC patients.

Keywords: Colorectal cancer; Direct bilirubin; Survival analysis; Total bile acid; Total bilirubin.

Fig. 1

X-tile analyses of 3-year OS was performed using patients’ data to determine the optimal cut-off value for TBIL, DBIL, and TBA. X-tile analyses of TBIL (a), DBIL (b), and TBA (c) levels in CRC patients. X-tile plots for patients are shown in the left panels; black circles highlight the optimal cutoff values, which are also shown in histograms (middle panels). Kaplan-Meier plots are presented in right panels, and in terms of OS, the best cut-off values of TBIL, DBIL and TBA are 6.4 μmol/l, 12.8 μmol/l and 7.1 μmol/l, respectively

Fig. 2

X-tile analyses of 3-year DFS was performed using patients’ data to determine the optimal cut-off value for TBIL, DBIL, and TBA. X-tile analyses of TBIL (a), DBIL (b), and TBA (c) levels in CRC patients. X-tile plots for patients are shown in the left panels; black circles highlight the optimal cutoff values, which are also shown in histograms (middle panels). Kaplan-Meier plots are presented in right panels, and in terms of DFS, the best cut-off values of TBIL, DBIL and TBA are 5.2 μmol/l, 13.1 μmol/l and 6.8 μmol/l, respectively

Fig. 3

Nomogram for predicting CRC patient outcomes. Nomograms conveyed the results of prognostic models using clinicopathological characteristics and pretreatment inflammatory biomarkers to predict OS (a) and DFS (b) of patients with CRC. The Harrell’s c-indexes for OS and DFS prediction were 0.819 (95% CI: 0.806–0.832) and 0.835 (95% CI: 0.822–0.849), respectively

Fig. 4

Calibration curves. Calibration curves for 3-year OS (a) and 3-year DFS (b) using nomograms with clinicopathological characteristics and pretreatment inflammatory biomarkers are shown. The 45-degree reference line represents a perfect match between observed and predicted values