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. 2021 Sep 28:11:731989.
doi: 10.3389/fonc.2021.731989. eCollection 2021.

Prognostic Value of Serum Osteoprotegerin Level in Patients With Hepatocellular Carcinoma Following Surgical Resection

Chihao Zhang  1 , Jiayun Lin  1 , Xiaochun Ni  1 , Hongjie Li  1 , Lei Zheng  1 , Zhifeng Zhao  1 , Xiaoliang Qi  1 , Haizhong Huo  1 , Xiaolou Lou  1 , Qiang Fan  1 , Meng Luo  1
Affiliations

Prognostic Value of Serum Osteoprotegerin Level in Patients With Hepatocellular Carcinoma Following Surgical Resection

Chihao Zhang et al. Front Oncol. .

Abstract

Background: Multiple studies have reported that tissue or serum osteoprotegerin (OPG) level is a prognostic factor for patients with cancer. However, little is known about the role of serum OPG in hepatocellular carcinoma (HCC). In this study, we aimed to investigate whether serum OPG concentration has an effect on HCC patients' prognosis.

Methods: A total of 386 eligible HCC patients undergoing radical hepatectomy were enrolled from Shanghai Ninth People's Hospital and Zhongshan Hospital between 2010 and 2018. Kaplan-Meier curves, Cox regression model, and the restricted mean survival time (RMST) were used to estimate the association of OPG and HCC patients' survival outcome. In addition, sensitivity analyses were carried out including subgroup analysis and propensity score matching (PSM).

Results: Patients were separated into two groups according to the cut-off value of OPG calculated by X-tile. Multivariate Cox analysis showed that patients with high OPG level had worse overall survival (OS) (HR: 1.93; 95% CI: 1.40-2.66, p<0.001) and disease-free survival (DFS) (HR: 1.85; 95% CI: 1.39-2.47, p<0.001) before matching. On average, RMST ratio between high and low OPG turned out to be 0.797 (95% CI: 0.716-0.887, p<0.001). In the matched population, we found that OPG level was negatively associated with OS (HR: 1.85; 95% CI: 1.25-2.74, p=0.002) and DFS (HR: 1.71; 95% CI: 1.20-2.44, p=0.003). In addition, a similar trend was further confirmed by subgroup analyses.

Conclusion: In a word, HCC patients with high OPG level had poorer survival rates compared with HCC patients with low OPG level. This factor could act as a potential prognostic predictor for HCC patients who underwent radical resection in the future.

Keywords: RANKL; disease-free survival; hepatocellular carcinoma; osteoprotegerin; overall survival.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Comparison of overall survival (A) and disease-free survival (B) between patients with high and low serum levels in the unmatched population.
Figure 2
Figure 2
Forest plot showing the effect of serum OPG levels on overall survival in HCC patients stratified by different clinicopathological factors before matching. HR>1 and p<0.05 suggested that higher OPG levels in serum were associated with poorer survival outcome.
Figure 3
Figure 3
Forest plot showing the effect of serum OPG levels on disease-free survival in HCC patients stratified by different clinicopathological factors before matching. HR>1 and p<0.05 suggested that higher OPG levels in serum were associated with poorer survival outcome.
Figure 4
Figure 4
Comparison of overall survival (A) and disease-free survival (B) between patients with high and low serum levels in the matched population.
Figure 5
Figure 5
Receiver operating characteristic (ROC) curve and its corresponding AUCs for the models with or without OPG in terms of OS (A) and DFS (B).
Figure 6
Figure 6
The effect of OPG on HCC patients’ OS (A, B) and DFS (C, D) stratified by AFP and GGT.
Figure 7
Figure 7
Receiver operating characteristic (ROC) curve of OPG, AFP and GGT in terms of OS (A) and DFS (B) and its corresponding AUCs.
See this image and copyright information in PMC

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