Dataset Information

Circulating Levels of PAI-1 and SERPINE1 4G/4G Polymorphism Are Predictive of Poor Prognosis in HCC Patients Undergoing TACE.

ABSTRACT: Although several molecular markers have been proposed as prognostic of disease progression in Hepatocellular carcinoma (HCC), predictive markers of response to treatment are still unsatisfactory. Here, we propose a genetic polymorphism as a potential predictive factor of poor prognosis in HCC patients treated with transcatheter arterial chemoembolization (TACE). In particular, we show that the guanosine insertion/deletion polymorphism in the promoter region of SERPINE1 gene at the -675 bp position, named 4G/4G, predicts poor prognosis in a cohort of 75 patients with HCC undergoing TACE. By a combination of ELISA and SERPINE1 promoter study, we found that the presence of elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) in patients with 4G/4G genotype is significantly associated with reduced overall survival compared to patients with 5G/5G or 4G/5G genotype in HCC patients after TACE. Our analysis provided evidence that variation in SERPINE1 gene plays a role in defining the outcome in patients treated with TACE. In addition to a poor disease outcome, the 4G/4G variant represents an unfavorable predictive factor for response to chemotherapy as well.

SUBMITTER: Divella R

PROVIDER: S-EPMC4562977 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Circulating Levels of PAI-1 and SERPINE1 4G/4G Polymorphism Are Predictive of Poor Prognosis in HCC Patients Undergoing TACE.

Divella Rosa R Daniele Antonella A Abbate Ines I Savino Eufemia E Casamassima Porzia P Sciortino Giancarlo G Simone Giovanni G Gadaleta-Caldarola Gennaro G Fazio Vito V Gadaleta Cosimo Damiano CD Sabbà Carlo C Mazzocca Antonio A

Translational oncology 20150801 4

Although several molecular markers have been proposed as prognostic of disease progression in Hepatocellular carcinoma (HCC), predictive markers of response to treatment are still unsatisfactory. Here, we propose a genetic polymorphism as a potential predictive factor of poor prognosis in HCC patients treated with transcatheter arterial chemoembolization (TACE). In particular, we show that the guanosine insertion/deletion polymorphism in the promoter region of SERPINE1 gene at the -675 bp positi ...[more]

PMID: 26310373

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Project description:BackgroundThe delayed percentage attenuation ratio (DPAR) was recently identified as a novel predictor of an early complete response in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). In this study, we aimed to validate the role of DPAR as a predictive biomarker for short-, mid-, and long-term outcomes after TACE.MethodsWe retrospectively reviewed laboratory and imaging data for 103 treatment-naïve patients undergoing initial TACE treatment at our tertiary care center between January 2016 and November 2020. DPAR and other washin and washout indices were quantified in the triphasic computed tomography performed before the initial TACE. The correlation of DPAR and radiologic response was investigated. Furthermore, the influence of DPAR on the 6-, 12-, 18-, and 24-month survival rates and the median overall survival (OS) was compared to other established washout indices and estimates of tumor burden and remnant liver function.ResultsThe DPAR was significantly of the target lesions (TLs) with objective response to TACE after the initial TACE session was significantly higher compared to patients with stable disease (SD) or progressive disease (PD) (125 (IQR 118-134) vs 110 (IQR 103-116), p < 0.001). Furthermore, the DPAR was significantly higher in patients who survived the first 6 months after TACE (122 vs. 115, p = 0.04). In addition, the number of patients with a DPAR > 120 was significantly higher in this group (n = 38 vs. n = 8; p = 0.03). However, no significant differences were observed in the 12-, 18-, and 24-month survival rates after the initial TACE. Regarding the median OS, no significant difference was observed for patients with a high DPAR compared to those with a low DPAR (18.7 months vs. 12.7 months, p = 0.260).ConclusionsOur results confirm DPAR as the most relevant washout index for predicting the short-term outcome of patients with HCC undergoing TACE. However, DPAR and the other washout indices were not predictive of mid- and long-term outcomes.

Project description:BACKGROUND:The E2F family of transcription factor 2 (E2F2) plays an important role in the development and progression of various tumors, but its association with hepatocellular carcinoma (HCC) remains unknown. Our study aimed to investigate the role and clinical significance of E2F2 in HCC. METHODS:HCC raw data were extracted from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression were applied to analyze the relationship between the expression of E2F2 and clinicopathologic characteristics. Cox regression and Kaplan-Meier were employed to evaluate the correlation between clinicopathologic features and survival. The biological function of E2F2 was annotated by Gene Set Enrichment Analysis (GSEA). RESULTS:The expression of E2F2 was increased in HCC samples. The expression of elevated E2F2 in HCC samples was prominently correlated with histologic grade (OR?=?2.62 for G3-4 vs. G1-2, p?=?1.80E-05), clinical stage (OR?=?1.74 for III-IV vs. I-II, p?=?0.03), T (OR?=?1.64 for T3-4 vs.T1-2, p?=?0.04), tumor status (OR?=?1.88 for with tumor vs. tumor free, p?=?3.79E-03), plasma alpha fetoprotein (AFP) value (OR?=?3.18 for AFP???400 vs AFP<20, p?=?2.16E-04; OR?=?2.50 for 20???AFP<400 vs AFP<20, p?=?2.56E-03). Increased E2F2 had an unfavorable OS (p?=?7.468e-?05), PFI (p?=?3.183e-?05), DFI (p?=?0.001), DSS (p?=?4.172e-?05). Elevated E2F2 was independently bound up with OS (p?=?0.004, hazard ratio [HR]?=?2.4 (95% CI [1.3-4.2])), DFI (P?=?0.029, hazard ratio [HR]?=?2.0 (95% CI [1.1-3.7])) and PFI (P?=?0.005, hazard ratio [HR]?=?2.2 (95% CI [1.3-3.9])). GSEA disclosed that cell circle, RNA degradation, pyrimidine metabolism, base excision repair, aminoacyl tRNA biosynthesis, DNA replication, p53 signaling pathway, nucleotide excision repair, ubiquitin-mediated proteolysis, citrate cycle TCA cycle were notably enriched in E2F2 high expression phenotype. CONCLUSIONS:Elevated E2F2 can be a promising independent prognostic biomarker and therapeutic target for HCC. Additionally, cell cycle, pyrimidine metabolism, DNA replication, p53 signaling pathway, ubiquitin-mediated proteolysis, the citrate cycle TCA cycle may be the key pathway by which E2F2 participates in the initial and progression of HCC.

Project description:ObjectivesThis study aims to compare the safety and effectiveness between transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) and conventional TACE (cTACE) using lipiodol-based regimens in HCC patients with a transjugular intrahepatic portosystemic shunt (TIPS).MethodsThis retrospective study included patients with patent TIPS who underwent TACE from January 2013 to January 2019 that received either DEB-TACE (DEB-TACE group, n = 57) or cTACE (cTACE group, n = 62). The complications, liver toxicity, overall survival (OS), time to progression (TTP), and objective response rate (ORR) were compared between the groups.ResultsAltogether, 119 patients (50 ± 11 years, 107 men) were evaluated. The incidence of adverse events, including abdominal pain within 7 days (45.6% vs 79.0%, p < 0.001) and hepatic failure within 30 days (5.3% vs 19.4%, p = 0.027), were significantly lower in the DEB-TACE group than in the cTACE group. Compared to the cTACE group, the DEB-TACE group also showed mild liver toxicities in terms of increased total bilirubin (8.8% vs 22.6%), alanine aminotransferase (5.3% vs 21.0%), and aspartate aminotransferase (10.5% vs 29.0%) levels. The DEB-TACE group had better ORR than the cTACE group (70.2% vs 50.0%). The median OS and TTP were longer in the DEB-TACE group (11.4 vs 9.1 months, hazard ratio [HR] = 2.46, p < 0.001; 6.9 vs 5.2 months, HR = 1.47, p = 0.045). Multivariable analysis showed that α-fetoprotein levels, Barcelona clinic liver cancer stage, and treatment allocation were independent predictors of OS.ConclusionDEB-TACE is safe and effective in HCC patients with a TIPS and is potentially superior to cTACE in terms of complications, liver toxicities, OS, TTP, and ORR.Key points• DEB-TACE is safe and effective in HCC patients after a TIPS procedure. • DEB-TACE improves overall survival, objective response rate, and liver toxicities and is non-inferior to cTACE in terms of time to progression. • DEB-TACE might be a potential new therapeutic option for HCC patients with TIPS.

Dataset Information

Circulating Levels of PAI-1 and SERPINE1 4G/4G Polymorphism Are Predictive of Poor Prognosis in HCC Patients Undergoing TACE.

Publications

Circulating Levels of PAI-1 and SERPINE1 4G/4G Polymorphism Are Predictive of Poor Prognosis in HCC Patients Undergoing TACE.

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