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Circulating pro- and anti-angiogenic factors in multi-stage liver disease and hepatocellular carcinoma progression.

ABSTRACT: To date, few studies have carried out a simultaneous determination of multiple pro- and anti-angiogenic factors during liver diseases progression. This study investigated the dynamic change in circulating angiogenic factors in multi-step carcinogenesis and hepatocellular carcinoma (HCC) progression. Serum levels of major pro-angiogenic [Vascular endothelial growth factor (VEGF), Basic fibroblast growth factor (b-FGF)] and anti-angiogenic [Thrombospondin-1 (TSP-1), Endostatin] factors were identified by enzyme-linked immunosorbent assay and correlated with liver diseases progression and outcomes of HCC patients undergoing transarterial chemo-embolization. A total of 240 patients (156 HCC, 37 cirrhosis and 47 chronic hepatitis) were enrolled in this study. While progressing from chronic hepatitis, cirrhosis to HCC, VEGF and b-FGF levels showed a significant change. Particularly, b-FGF yielded the highest AUROC value for a diagnosis of HCC and its distinction from other disease groups. A trend towards increasing VEGF levels was observed from Child-Pugh class A, B to C. VEGF and TSP-1 levels increased with the advance of cancer stage, with a remarkable increase in TSP-1 at an intermediate stage. Pretreatment levels of VEGF, TSP-1, and endostatin independently predicted the overall survival of patients. VEGF and TSP-1 levels correlated with progression-free survival. Our study demonstrated the dynamic angiogenic switch and the roles that individual pro- and anti-angiogenic factors contribute to carcinogenesis and HCC progression during the course of multi-step liver diseases. These imply the future possibility of testing pro- and anti-angiogenic panels as a diagnostic marker and a guide in decision-making about upcoming targeted therapies.

SUBMITTER: Joo YY

PROVIDER: S-EPMC6591389 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Circulating pro- and anti-angiogenic factors in multi-stage liver disease and hepatocellular carcinoma progression.

Joo Yu Young YY Jang Jeong Won JW Lee Sung Won SW Yoo Sun Hong SH Kwon Jung Hyun JH Nam Soon Woo SW Bae Si Hyun SH Choi Jong Young JY Yoon Seung Kew SK

Scientific reports 20190624 1

To date, few studies have carried out a simultaneous determination of multiple pro- and anti-angiogenic factors during liver diseases progression. This study investigated the dynamic change in circulating angiogenic factors in multi-step carcinogenesis and hepatocellular carcinoma (HCC) progression. Serum levels of major pro-angiogenic [Vascular endothelial growth factor (VEGF), Basic fibroblast growth factor (b-FGF)] and anti-angiogenic [Thrombospondin-1 (TSP-1), Endostatin] factors were identi ...[more]

PMID: 31235729

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Project description:BackgroundThe combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic agents has shown promising efficacy in unresectable hepatocellular carcinoma (HCC), but until now no clinical prognostic models or predictive biomarkers have been established.MethodsFrom 2016 to 2021, a total of 258 HCCs treated with ICIs and tyrosine kinase inhibitors (TKIs) were retrospectively enrolled, as the study cohort. Patients' baseline data was extracted by least absolute and shrinkage selection operator (LASSO) and Cox regression. Finally, a prognostic model in the form of nomogram was developed. Model performance was assessed in terms of discrimination, calibration, and clinical utility. A 5-fold cross-validation was used to evaluate the internal repeatability of the model. In addition, the patient cohort was divided into three subgroups according to nomogram scores. Their survivals were estimated by Kaplan-Meier methods and the differences were analyzed using log-rank tests.ResultsSeven clinical parameters were selected: Eastern Cooperative Oncology Group performance status (ECOG PS), combination of transarterial chemoembolization (TACE), extrahepatic metastasis (EHM), platelet to lymphocyte ratio (PLR), alanine aminotransferase (ALT), alpha-fetoprotein (AFP), and Child-Pugh score. The model had an area under the curve (AUC) of 0.777 at 1 year and 0.772 at 2 years. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) showed that the discrimination, consistency and applicability of the model were good. In addition, cross-validation validated the discrimination of the model, and the C index value of the model is 0.7405. The median overall survival (OS) of the high-, medium- and low-risk subgroups was 7.58, 17.50 and 53.17 months, respectively, with a significant difference between the groups (P < 0.0001).ConclusionWe developed a comprehensive and simple prognostic model for the combination of ICIs plus TKIs. And it may predict the efficacy of the combination regimen for unresectable HCC.

Dataset Information

Circulating pro- and anti-angiogenic factors in multi-stage liver disease and hepatocellular carcinoma progression.

Publications

Circulating pro- and anti-angiogenic factors in multi-stage liver disease and hepatocellular carcinoma progression.

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