Dataset Information

A scoring model based on neutrophil to lymphocyte ratio predicts recurrence of HBV-associated hepatocellular carcinoma after liver transplantation.

ABSTRACT:

Background

Neutrophil to lymphocyte ratio (NLR) has been proposed to predict prognosis of hepatocellular carcinoma (HCC). However, the cut-off values are empirical. We determined the optimal cut-off value to predict HCC recurrence after liver transplantation (LT) and further established a scoring model based on NLR.

Methodology/principal findings

We analyzed the outcome of 101 HBV-associated HCC patients undergoing LT. Preoperative risk factors for tumor recurrence were evaluated by univariate analysis. By using ROC analysis, NLR?3 was considered elevated. The disease-free survival (DFS) and overall survival (OS) for patients with high NLR was significantly worse than that for patients with normal NLR (the 5-year DFS and OS of 28.5% and 19.5% vs. 64.9% and 61.8%, respectively; P<0.001). Univariate analysis revealed that tumor size >5 cm, tumor number >3, macrovascular invasion, AFP?400 µg/L, NLR?3, and HBV-DNA level >5 log10 copies/mL were preoperative predictors of DFS. Cox regression analysis showed macrovascular invasion, tumor number, and high NLR were independent prognostic factors. We then established a preoperative prognostic score based on multivariate analysis. Each factor was given a score of 1. Area under the ROC curve of the score was 0.781. All nine patients with score 3 developed recurrence within 6 months after LT. Of 71 patients without vascular invasion, three patients with both tumor number >3 and NLR?3 developed recurrence within 14 months after LT while the 5-year DFS and OS for patients with a score of 0 or 1 were 68.1% and 62.8%, respectively.

Conclusions/significance

Preoperative elevated NLR significantly increases the risk of recurrence in patients underwent LT for HCC. Patients with both NLR?3 and tumor number >3 are not a good indication for LT. Our score model may aid in the selection of patients that would most benefit from transplantation for HCC.

SUBMITTER: Wang GY

PROVIDER: S-EPMC3180380 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A scoring model based on neutrophil to lymphocyte ratio predicts recurrence of HBV-associated hepatocellular carcinoma after liver transplantation.

Wang Guo-Ying GY Yang Yang Y Li Hua H Zhang Jian J Jiang Nan N Li Min-Ru MR Zhu Huan-Bing HB Zhang Qi Q Chen Gui-Hua GH

PloS one 20110926 9

<h4>Background</h4>Neutrophil to lymphocyte ratio (NLR) has been proposed to predict prognosis of hepatocellular carcinoma (HCC). However, the cut-off values are empirical. We determined the optimal cut-off value to predict HCC recurrence after liver transplantation (LT) and further established a scoring model based on NLR.<h4>Methodology/principal findings</h4>We analyzed the outcome of 101 HBV-associated HCC patients undergoing LT. Preoperative risk factors for tumor recurrence were evaluated ...[more]

PMID: 21966488

Similar Datasets

Project description:Background: Liver transplantation (LT) for Hepatocellular carcinoma (HCC) can be offered to patients beyond Milan criteria. However, there are currently no molecular markers that can be used on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to identify proteins on HCC explant predictive of recurrence post-transplant, thereby guiding surveillance strategies and identifying patients beyond Milan criteria who would fare well following LT. Methods: LT recipients who had been transplanted at the University Health Network for HCC beyond Milan criteria in the context of Hepatitis B cirrhosis were identified. Snap-frozen samples from the dominant tumors of recurrent (N=7) and non-recurrent (N=4) patients were analyzed using LC-MS/MS on a Q-Exactive Plus mass spectrometer to delineate a distinctive proteomic signature. These tumors were also profiled by a Human Gene 2.0 ST microarray platform to identify a transcriptomic signature predictive of recurrence and analyzed with R packages. STRING database was used to characterize the implicated pathways. Kaplan-Meier estimator was used to generate a combined proteomic/transcriptomic signature predictive of HCC recurrence in patients with HCC beyond Milan criteria at time of LT. Significantly predictive proteins were verified and internally validated by immunoblotting or immunohistochemistry. Results: A total of 79 proteins and 636 genes were significantly differentially expressed in recurrent HCC, compared to non-recurrent (p<0.05). Among these, LGALS3, LGALS3BP, HAL, THBS1, and BLMH, were significantly increased in recurrent HCC at the protein and gene expression level. In turn, ALDH1A1 protein and gene expression were significantly decreased in recurrent HCC. Univariate survival analysis depicted ALDH1A1 (HR=0.084, 95%CI 0.01-0.68, p=0.02), LGALS3BP (HR=7.14, 95%CI 1.20-42.96, p=0.03), and LGALS3 (HR=2.89, 95%CI 1.01-8.3, p=0.049) as the key dysregulated proteins and genes in the patients with HCC recurrence versus those with non-recurrence by both proteomic and transcriptomic analysis. Decreased ALDH1A1 and significantly increased LGALS3 protein expression in recurrent HCC was verified by immunoblotting. Increased LGALS3BP protein expression in recurrent HCC was orthogonally verified and validated by immunohistochemistry in 30 independent HCC samples. Conclusion: Protein and gene expression of the cancer stem cell marker ALDH1A1 was protective against cancer recurrence in patients transplanted for HCC beyond Milan criteria. Conversely, increased expression of LGALS3 and LGALS3BP on explant was significantly predictive of post-transplant recurrence. These findings were internally validated, suggesting potential utility in identifying patients with HCC beyond Milan who would clearly benefit from transplant with limited recurrence risk and guiding post-transplant surveillance.

Project description:Tumor-infiltrating immune cells are relevant prognostic and immunotherapeutic targets in hepatocellular carcinoma (HCC). Mast cells play a key role in allergic response but may also be involved in anticancer immunity. Digital morphometric analysis of patient tissue sections has become increasingly available for clinical routine and provides unbiased quantitative data. Here, we apply morphometric analysis of mast cells to retrospectively evaluate their relevance for HCC recurrence in patients after orthotopic liver transplantation (OLT). A total of 173 patients underwent OLT for HCC at the Medical University of Vienna (21 women, 152 men; 55.2 ± 7.9 years; 74 beyond Milan criteria, 49 beyond up-to-7 criteria for liver transplantation). Tissue arrays from tumors and corresponding surrounding tissues were immunohistochemically stained for mast cell tryptase. Mast cells were quantified by digital tissue morphometric analysis and correlated with HCC recurrence. Mast cells were detected in 93% of HCC tumors and in all available surrounding liver tissues. Tumor tissues revealed lower mast cell density than corresponding surrounding tissues (P < 0.0001). Patients lacking intratumoral mast cells (iMCs) displayed larger tumors and higher tumor recurrence rates both in the whole cohort (hazard ratio [HR], 2.74; 95% confidence interval [CI], 1.09-6.93; P = 0.029) and in patients beyond transplant criteria (Milan HR, 2.81; 95% CI, 1.04-7.62; P = 0.01; up-to-7 HR, 3.58; 95% CI, 1.17-10.92; P = 0.02). Notably, high iMC identified additional patients at low risk classified outside the Milan and up-to-7 criteria, whereas low iMC identified additional patients at high risk classified within the alpha-fetoprotein French and Metroticket criteria. iMCs independently predicted tumor recurrence in a multivariate Cox regression analysis (Milan HR, 2.38; 95% CI, 1.16-4.91; P = 0.019; up-to-7 HR, 2.21; 95% CI, 1.05-4.62; P = 0.035). Conclusion: Hepatic mast cells might be implicated in antitumor immunity in HCC. Morphometric analysis of iMCs refines prognosis of HCC recurrence after liver transplantation.

Dataset Information

A scoring model based on neutrophil to lymphocyte ratio predicts recurrence of HBV-associated hepatocellular carcinoma after liver transplantation.

Background

Methodology/principal findings

Conclusions/significance

Publications

A scoring model based on neutrophil to lymphocyte ratio predicts recurrence of HBV-associated hepatocellular carcinoma after liver transplantation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets