Using a novel gene signature for predicting the efficacy of the transarterial chemoembolization in patients with hepatocellular carcinoma.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE104580 | GEO | 2020/10/01
REPOSITORIES: GEO
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Project description:Hepatocellular carcinoma (HCC) often receives transarterial chemoembolization (TACE), yet clinical benefit is limited by resistance driven by ischemia-induced adaptations. This study explains how transketolase (TKT) in the pentose phosphate pathway (PPP) modulates HCC progression and TACE refractoriness, and clarifies its mechanistic connection to oncogenic signaling.
2026-03-07 | GSE322668 | GEO
Project description:These paired HCC and non-tumorous liver tissues were used to determine highly differentially expressed genes in HCC and non-tumorous liver tissue. Hepatocellular carcinoma (HCC) is a malignancy with poor survival outcome. Genes showing extreme differential expression between paired human HCC and adjacent non-tumorous liver tissue were investigated. PLVAP was identified as a gene specifically expressed in vascular endothelial cells of HCC but not in non-tumorous liver tissues. This finding was confirmed by RT-PCR analysis of micro-dissected cells and immunohistochemical staining of tissue sections. A recombinant monoclonal anti-PLVAP Fab fragment co-expressing extracellular domain of human tissue factor (TF) was developed. The potential therapeutic effect and toxicity to treat HCC were studied using a Hep3B HCC xenograft model in SCID mice. Infusion of recombinant monoclonal anti-PLVAP Fab-TF into the tumor feeding artery induced tumor vascular thrombosis and extensive tumor necrosis at doses between 2.5 µg and 12 µg. Tumor growth was suppressed for 40 days after a single treatment. Systemic administration did not induce tumor necrosis. Little systemic toxicity was noted for this therapeutic agent. The results of this study suggest that anti-PLVAP Fab-TF may be used to treat HCC cases for which transcatheter arterial chemoembolization (TACE) is currently used, but without major drawbacks of TACE. Anti-PLVAP Fab-TF may improve therapeutic outcome and be a viable therapeutic agent in patients with more advanced disease and compromised liver function. Frozen hepatocellular carcinoma and adjacent non-tumorous liver tissues were used for gnee expression profiling study. Affymetrix U133A genechips were used for gene expression profiling. This dataset is part of the TransQST collection.
2015-01-01 | E-GEOD-60502 | biostudies-arrayexpress
Project description:These paired HCC and non-tumorous liver tissues were used to determine highly dfferentially expressed genes in HCC and non-tumorous liver tissue. Hepatocellular carcinoma (HCC) is a malignancy with poor survival outcome. Genes showing extreme differential expression between paired human HCC and adjacent non-tumorous liver tissue were investigated. PLVAP was identified as a gene specifically expressed in vascular endothelial cells of HCC but not in non-tumorous liver tissues. This finding was confirmed by RT-PCR analysis of micro-dissected cells and immunohistochemical staining of tissue sections. A recombinant monoclonal anti-PLVAP Fab fragment co-expressing extracellular domain of human tissue factor (TF) was developed. The potential therapeutic effect and toxicity to treat HCC were studied using a Hep3B HCC xenograft model in SCID mice. Infusion of recombinant monoclonal anti-PLVAP Fab-TF into the tumor feeding artery induced tumor vascular thrombosis and extensive tumor necrosis at doses between 2.5 µg and 12 µg. Tumor growth was suppressed for 40 days after a single treatment. Systemic administration did not induce tumor necrosis. Little systemic toxicity was noted for this therapeutic agent. The results of this study suggest that anti-PLVAP Fab-TF may be used to treat HCC cases for which transcatheter arterial chemoembolization (TACE) is currently used, but without major drawbacks of TACE. Anti-PLVAP Fab-TF may improve therapeutic outcome and be a viable therapeutic agent in patients with more advanced disease and compromised liver function.
2015-01-01 | GSE60502 | GEO
Project description:We performed a transcriptomic analysis of hepatocellular carcinomas (HCCs) and paired non-tumor biopsies to identify predictive biomarkers for response to transarterial chemoembolization (TACE). We identified several transcripts which are predictive of response to TACE.
| EGAS00001005558 | EGA
Project description:Using a novel gene signature for predicting the efficacy of the transarterial chemoembolization in patients with hepatocellular carcinoma.
| PRJNA413131 | ENA
Project description:Purpose:In recent years, increasing evidence has confirmed that exosomal circular RNAs (circRNAs) play a crucial role in the prognostic prediction and diagnosis of liver cancer （LC）. In this study, we first compared the expression patterns of exosomal circRNAs during transarterial chemoembolization (TACE). Methods:CircRNA-seq identified 390 differentially expressed circRNAs between the prior TACE and TACE1 groups and 489 differentially expressed circRNAs between the prior TACE and TACE2 groups. GO analysis of the differentially expressed circRNAs showed that they were associated with fatty acid metabolism, receptor binding and membrane protein complexes. KEGG pathway analysis predicted that protein digestion and absorption pathways were activated after TACE. And we screened out a novel gene , hsa_circRNA_G004213 (circ_G004213) was significantly upregulated after TACE (fold change >10, P<0.01). Further analysis found circ_G004213 significantly increased the cisplatin sensitivity of HepG2 cells and positively correlated with the prognosis of tumor-bearing mice. Based on the potential downstream miRNAs and mRNAs, the circRNA‐miRNA-mRNA network was constructed. Results: We demonstrated that circ_G004213 regulates cisplatin resistance via the miR-513b-5p/PRPF39 axis. Finally, our study confirmed that circ_G004213 was positively correlated with the prognosis of LC patients after TACE. Therefore, circ_G004213 may be used as an indicator for predicting the efficacy of TACE. Conclusions: Hsa_circRNA_G004213 Promotes Cisplatin Sensitivity by Regulating miR-513b-5p/PRPF39 in Liver Cancer.
2021-01-21 | GSE165183 | GEO
Project description:Background & Aims: Hepatocellular carcinoma (HCC) is the second most lethal cancer due to lack of effective therapies. Although promising, HCC molecular classification, which enriches potential responders to specific therapies, has not yet been assessed in clinical trials of anti-HCC drugs. We aimed to overcome these challenges by developing clinicopathological surrogate indices of HCC molecular classification. Methods: HCC classification defined in our previous transcriptome meta-analysis (S1, S2, and S3 subclasses) was implemented in an FDA-approved diagnostic platform (Elements assay, NanoString). Ninety-six HCC tumors (training set) were assayed to develop molecular subclass-predictive indices based on clinicopathological features, which were independently validated in 99 HCC tumors (validation set). Molecular deregulations associated with the histopathological features were determined by pathway analysis. Sample sizes for HCC clinical trials enriched with specific molecular subclasses were determined. Results: HCC subclass-predictive indices were: steatohepatitic (SH)-HCC variant and immune cell infiltrate for S1 subclass, macrotrabecular/compact pattern, lack of pseudoglandular pattern, and high serum alpha-fetoprotein (>400 ng/mL) for S2 subclass, and microtrabecular pattern, lack of SH-HCC and clear cell variants, and lower histological grade for S3 subclass. Macrotrabecular/compact pattern, a predictor of S2 subclass, was associated with activation of therapeutically targetable oncogene YAP and stemness markers EPCAM/KRT19. BMP4 was associated with pseudoglandular pattern. Subclass-predictive indices-based patient enrichment reduced clinical trial sample sizes from 121, 184, and 53 to 30, 43, and 22 for S1, S2, and S3 subclass-targeting therapies, respectively. Conclusions: HCC molecular subclasses can be enriched by clinicopathological indices tightly associated with deregulation of therapeutically targetable molecular pathways.
2015-06-17 | GSE59548 | GEO
Project description:Both drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) are recommended for unresectable colorectal liver metastases (CRLM) treatment. However, the combined application of DEB-TACE and HAIC is not widely accepted. The aim of this single-center retrospective study was to evaluate the efficacy and safety of Irinotecan-eluting HepaSphere chemoembolization combined with HAIC for unresectable CRLM
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Project description:Immune checkpoint inhibitor (ICI) resistance in advanced hepatocellular carcinoma (HCC)poses a major therapeutic challenge. Here, we report a phase 2 trial evaluating stereotactic bodyradiotherapy (SBRT) combined with the anti-PD-1 antibody sintilimab and bevacizumabbiosimilar (lBI305) to re-sensitize ICI-refractory HCC. Twenty-one patients with progressiveHCC after prior ICI therapy received SBRT (25-50 Gy in 5 fractions) followed by sintilimab(200 mg) and IBl305 (15 mgkg) every 3 weeks. The primary endpoint, objective response rate(ORR) in non-irradiated lesions, was 33.3% (7/21), with a disease control rate of66.7%(14/21)Median progression-free survival (PFS) was 6.2 months (95% CI 3.7-15.1), and estimatedmedian overall survival (OS) was 24.4 months (95% CI 9.2-NA). SBRT achieved 100% localcontrol, while grade >3 treatment-related adverse events occurred in 33.3% of patientsLongitudinal proteomic profiling revealed that responders exhibited lower baseline IFN-y (p0.025) and elevated IL-6 (p=0.002), with post-SBRT increases in IFN-y, IL-2, and IL-6correlating with improved outcomes. These findings demonstrate that SBRT synergizes withdual PD-1/VEGF blockade to overcome ICI resistance, potentially through radiation-inducedimmune remodeling. Biomarker dynamics highlight actionable targets for optimizingcombination therapies in anti-PD-1-refractory HCC.
2025-10-15 | PAD000004 | Pride
Project description:Vascular invasion is considered as the critical risk factors for tumor recurrence of hepatocellular carcinoma (HCC). To reveal the molecular mechanisms underlying macrovascular invasion (MaVI) and metastasis in HCC, we performed an iTRAQ based proteomic study to identify notably dysregulated proteins in 53 HCC patients with differential vascular invasion. In patients with MaVI, 47 proteins were significantly down-regulated in HCC tumor tissue. More importantly, 30 of them were not changed in HCC without MaVI. Gene ontology analysis of these 47 proteins shows the top 3 enriched pathways are urea cycle, gluconeogenesis and arginine biosynthetic process. We validated 9 remarkably dysregulated candidates in HCC patients with MaVI by Western blot, including 8 down-regulated proteins (CPS1, ASS1, ASL, ARG1, BHMT, DMGDH, Annexin A6 and CES1) and 1 up-regulated protein (CKAP4). Furthermore, dysregulation of CPS1, ASL and ARG1, key enzymes involved in urea cycle, together with Annexin A6 and CES1, major proteins in regulating cholesterol homeostasis and fatty acid ester metabolism were verified using immunohistochemical staining. The significant down-regulation of urea cycle generates clinically relevant proteomic signature in HCC patients with macrovascular invasion, which may provide possible insights into the molecular mechanisms of metastasis and new therapeutic targets of HCC.
2022-03-02 | PXD011846 | Pride