Dataset Information

Development of a Novel Inflammation-Based Index for Hepatocellular Carcinoma.

ABSTRACT:

Background

The aim of current study was to (1) construct and validate a novel hepatocellular carcinoma (HCC)-specific inflammatory index; (2) compare the performances of the Integrated Liver Inflammatory Score (ILIS) to existing 4 inflammatory indices in HCC; (3) explore the association between the inflammatory indices and systemic/intratumoral inflammatory markers.

Methods

Two cohorts from Hong Kong (HK; n = 1,315) and Newcastle (n = 574) were studied. A novel index was constructed from the HK training set (n = 627). The index was constructed from the training set by combing independent prognostic circulating parameters, followed by validating in the validation set of HK cohort (n = 688) and the Newcastle cohort. Its prognostic performance was compared to 4 inflammatory indices, namely, the neutrophil to lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutrition index, and systemic immune-inflammation index, were compared in the HK cohort. Circulating cytokines and intratumoral gene expression were analyzed in a subset of patients with available samples and correlated with the inflammatory indices.

Results

In the training set of the HK cohort, the ILIS, was generated: -0.057 × albumin (g/L) + 0.978 × log (Bilirubin, µmol/L) + 1.341 × log (alkaline phosphatase, IU/L) + 0.086 × Neutrophil (10⁹/L) + 0.301 × log (alpha-fetoprotein, µg/L). With cutoff of 2.60 and 3.87, the ILIS could categorize patients into 3 risk groups in the both validation cohorts. ILIS outperforms other inflammatory indices and remains an independent prognosticator for overall survival after adjustment with Barcelona Clinic Liver Cancer (hazard ratio 31.90, p < 0.001). The ILIS had the best prognostic performances as compared to other inflammatory indices. In exploratory analyses, the ILIS correlated with circulating inflammatory cytokines (e.g., IL-8) but not with any intratumoral inflammatory gene expression.

Conclusions

ILIS is an HCC-specific prognostic index built on 5 readily available blood parameters. Its versatility is validated both Eastern and Western population of HCC. The score is correlated with levels of circulating cytokines.

SUBMITTER: Chan SL

PROVIDER: S-EPMC7206612 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

Development of a Novel Inflammation-Based Index for Hepatocellular Carcinoma.

Chan Stephen Lam SL Wong Lin-Lee LL Chan Kwan-Chee Allen KA Chow Chit C Tong Joanna Hung-Man JH Yip Terry Cheuk-Fung TC Wong Grace Lai-Hung GL Chong Charing Ching-Ning CC Liu Po-Hong PH Chu Cheuk-Man CM Wong Vincent Wai-Sun VW To Ka-Fai KF Reeves Helen L HL Chan Anthony Wing-Hung AW

Liver cancer 20191121 2

<h4>Background</h4>The aim of current study was to (1) construct and validate a novel hepatocellular carcinoma (HCC)-specific inflammatory index; (2) compare the performances of the Integrated Liver Inflammatory Score (ILIS) to existing 4 inflammatory indices in HCC; (3) explore the association between the inflammatory indices and systemic/intratumoral inflammatory markers.<h4>Methods</h4>Two cohorts from Hong Kong (HK; <i>n</i> = 1,315) and Newcastle (<i>n</i> = 574) were studied. A novel index ...[more]

PMID: 32399431

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Project description:BackgroundLiver cancer is one of the most common malignancies worldwide. HCC (hepatocellular carcinoma) is the predominant pathological type of liver cancer, accounting for approximately 75-85 % of all liver cancers. Lipid metabolic reprogramming has emerged as an important feature of HCC. However, the influence of lipid metabolism-related gene expression in HCC patient prognosis remains unknown. In this study, we performed a comprehensive analysis of HCC gene expression data from TCGA (The Cancer Genome Atlas) to acquire further insight into the role of lipid metabolism-related genes in HCC patient prognosis.MethodsWe analyzed the mRNA expression profiles of 424 HCC patients from the TCGA database. GSEA(Gene Set Enrichment Analysis) was performed to identify lipid metabolism-related gene sets associated with HCC. We performed univariate Cox regression and LASSO(least absolute shrinkage and selection operator) regression analyses to identify genes with prognostic value and develop a prognostic model, which was tested in a validation cohort. We performed Kaplan-Meier survival and ROC (receiver operating characteristic) analyses to evaluate the performance of the model.ResultsWe identified three lipid metabolism-related genes (ME1, MED10, MED22) with prognostic value in HCC and used them to calculate a risk score for each HCC patient. High-risk HCC patients exhibited a significantly lower survival rate than low-risk patients. Multivariate Cox regression analysis revealed that the 3-gene signature was an independent prognostic factor in HCC. Furthermore, the signature provided a highly accurate prediction of HCC patient prognosis.ConclusionsWe identified three lipid-metabolism-related genes that are upregulated in HCC tissues and established a 3-gene signature-based risk model that can accurately predict HCC patient prognosis. Our findings support the strong links between lipid metabolism and HCC and may facilitate the development of new metabolism-targeted treatment approaches for HCC.

Dataset Information

Development of a Novel Inflammation-Based Index for Hepatocellular Carcinoma.

Background

Methods

Results

Conclusions

Publications

Development of a Novel Inflammation-Based Index for Hepatocellular Carcinoma.

Similar Datasets

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