A novel preoperative inflammation score system established for postoperative prognosis predicting of intrahepatic cholangiocarcinoma

Abstract

Background: Inflammation is implicated in tumorigenesis and has been reported as an important prognostic factor in cancers. In this study, we aimed to develop and validate a novel inflammation score (IFS) system based on 12 inflammatory markers and explore its impact on intrahepatic cholangiocarcinoma (ICC) survival after hepatectomy.

Methods: Clinical data of 446 ICC patients undergoing surgical treatment were collected from the Primary Liver Cancer Big Data, and then served as a training cohort to establish the IFS. Furthermore, an internal validation cohort including 175 patients was used as internal validation cohort of the IFS. A survival tree analysis was used to divide ICC patients into three groups (low-, median-, and high- IFS-score groups) according to different IFS values. Kaplan-Meier (KM) curves were used to compare the overall survival (OS) and recurrence-free survival (RFS) rates among three different groups. Cox regression analyses were applied to explore the independent risk factors influencing OS and RFS.

Results: In the training cohort, 149 patients were in the low-IFS-score group, 187 in the median-IFS-score group, and 110 in the high-IFS-score group. KM curves showed that the high-IFS-score group had worse OS and RFS rates than those of the low- and median-IFS-score groups (P < 0.001) in both the training and validation cohorts. Moreover, multivariable Cox analyses identified high IFS as an independent risk factor for OS and RFS in the training cohort. The area under the curve values for OS prediction of IFS were 0.703 and 0.664 in the training and validation cohorts, respectively, which were higher than those of the American Joint Committee on Cancer (AJCC) 7th edition TNM stage, AJCC 8th edition TNM stage, and the Child-Pugh score.

Conclusion: Our results revealed the IFS was an independent risk factor for OS and RFS in patients with ICC after hepatectomy and could serve as an effective prognostic prediction system in daily clinical practice.

Keywords: Intrahepatic cholangiocarcinoma; Liver resection; Prognosis; Systemic inflammation.

Fig. 1

Heatmap of correlation among the fifteen inflammatory markers (a). Correlation plot showing the specific correlation coefficient relationship among the fifteen inflammatory markers (b)

Fig. 2

Circle correlation plot showing the relationship among the fifteen inflammatory markers (a). Cut-off values of fifteen inflammatory markers and the univariable Cox prognosis analysis of those markers for OS (b)

Fig. 3

Survival tree analysis of OS in the training cohort and 2 point and 6 point were considered to be two best cut-off values

Fig. 4

Heatmap showing the distribution of 15 inflammatory markers’ values in the training cohort according to the different IFS values and different IFS groups

Fig. 5

KM curves of OS and RFS for patients with ICC in the training cohort (a and b). ROC curves of IFS system (c), and the time-dependent ROC curves for IFS system and other clinical staging systems in the training cohorts (d)

Fig. 6

KM curves of OS and RFS for patients with ICC in the internal validation cohort (a and b). ROC curves of IFS system (c), and the time-dependent ROC curves for IFS system and other clinical staging systems in the internal validation cohort (d)