Albumin-to-Alkaline Phosphatase Ratio is an Independent Prognostic Indicator in Combined Hepatocellular and Cholangiocarcinoma

Background: The clinical significance of Albumin-to-Alkaline Phosphatase Ratio (AAPR) has been discussed in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). The aim of this study is to clarify the prognostic value of AAPR in patients with combined hepatocellular and cholangiocarcinoma (cHCC-CCA). Methods: A total of 267 patients pathologically diagnosed as Allen type C cHCC-CCA in our institution were retrospectively enrolled and randomly divided into the training (N=187) cohort and validation (N=80) cohort. The prognostic value of AAPR was evaluated and validated. An AAPR-based nomogram was constructed and its prediction performance was assessed. Results: We identified 0.43 as the optimal threshold value of AAPR by the X-tile software. In the training cohort, the median overall survival (OS) of patients with AAPR < 0.43 was significant shorter than that of those with AAPR ≥ 0.43(15.8 months vs 35 months, respectively, P < 0.001). Univariate and multivariate analyses demonstrated that AAPR was a strong indicator of OS. The concordance index (C-index), receiver operating characteristic (ROC) curves, likelihood ratio tests (LAT), Akaike information criteria (AIC) and decision curve analysis (DCA) demonstrated that AAPR outperformed the Child-Pugh (CP) grade and albumin-bilirubin (ALBI) grade in predicting OS. These findings were further verified in the validation cohort. The AAPR-based nomogram achieved C-index values of 0.76 (95%CI: 0.71-0.81) in the training cohort and 0.69 (95%CI: 0.60-0.78) in the validation cohort, which presented significant superiority to TNM stage. Conclusions: Preoperative AAPR is an independent prognostic predictor in cHCC-CCA. The AAPR-based nomogram contributes to personalized prognosis prediction and clinical decision making for cHCC-CCA.

Keywords: Albumin-to-Alkaline Phosphatase Ratio; combined hepatocellular and cholangiocarcinoma; overall survival; serum biomarker.