Identification and validation of a plasma metabolomics-based model for risk stratification of intrahepatic cholangiocarcinoma

Abstract

Background: Liver resection is the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC) while the postoperative prognosis varies greatly, with no recognized biomarker. We aimed to identify the plasma metabolomic biomarkers that could be used for preoperative risk stratification of ICC patients.

Methods: 108 eligible ICC patients who underwent radical surgical resection between August 2012 and October 2020 were enrolled. Patients were randomly divided into a discovery cohort (n = 76) and a validation cohort (n = 32) by 7:3. Metabolomics profiling of preoperative plasma was performed and clinical data were collected. The least absolute shrinkage and selection operator (LASSO) regression, Cox regression, and receiver operating characteristic (ROC) analyses were used to screen and validate the survival-related metabolic biomarker panel and construct a LASSO-Cox prediction model.

Results: 10 survival-related metabolic biomarkers were used for construction of a LASSO-Cox prediction model. In the discovery and validation cohorts, the LASSO-Cox prediction model achieved an AUC of 0.876 (95%CI: 0.777-0.974) and 0.860 (95%CI: 0.711-1.000) in evaluating 1-year OS of ICC patients, respectively. The OS of ICC patients in the high-risk group was significantly worse than that in the low-risk group (discovery cohort, p < 0.0001; validation cohort: p = 0.041). Also, the LASSO-Cox risk score (HR 2.43, 95%CI: 1.81-3.26, p < 0.0001) was a significant independent risk factor associated with OS.

Conclusions: The LASSO-Cox prediction model has potential as an important tool in evaluating the OS of ICC patients after surgical resection and can be used as prediction tools to implement the best treatment options that could result in better outcomes.

Keywords: Intrahepatic cholangiocarcinoma; Metabolomics; Prognosis; Risk stratification.