Plasma and tumoral glypican‐3 levels are correlated in patients with hepatitis C virus‐related hepatocellular carcinoma

Shimizu, Yasuhiro; Mizuno, Shoichi; Fujinami, Norihiro; Suzuki, Toshihiro; Saito, Keigo; Konishi, Masaru; Takahashi, Shinichiro; Gotohda, Naoto; Tada, Toshifumi; Toyoda, Hidenori; Kumada, Takashi; Miura, Masahiro; Suto, Kouzou; Yamaji, Taiki; Matsuda, Takahisa; Endo, Itaru; Nakatsura, Tetsuya

doi:10.1111/cas.14251

Cited by 12 publications

(11 citation statements)

References 45 publications

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“…In the GPC3‐negative group, 5/6 cases (83.3%) survived beyond 5 y, and survival was high regardless of CTL induction. Plasma GPC3 concentration was measured 1‐mo post‐operation, and a concentration of ≥6.8 pg/mL was defined as positive for plasma GPC3 52 . When postoperative plasma levels of GPC3 were included in the analysis, 12 patients were found to be positive for GPC3 in plasma and IHC staining and, in this group, OS beyond 5 y was shown in 9/12 (75%) patients (Figure 5B).…”

Section: Resultsmentioning

confidence: 99%

“…All liver specimens were prepared from surgically resected tumors. GPC3 IHC staining, CTL induction after vaccination, and plasma GPC3 were studied, as previously described 47,52,53 . Specimens were stained with hematoxylin and eosin or monoclonal antibodies (dilution 1:300) raised against GPC3 (clone 1G12; 1:200 dilution; BioMosaics) in accordance with the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Plasma GPC3 concentration was measured 1-mo post-operation, and a concentration of ≥6.8 pg/mL was defined as positive for plasma GPC3. 52 When postoperative plasma levels of GPC3 were included in the analysis, 12 patients were found to be positive for GPC3 in plasma and IHC staining and, in this group, OS beyond 5 y was shown in 9/12 (75%) patients ( Figure 5B). Here, 7 of 9 (77.8%) patients who survived beyond 5 y were CTL positive, and 1 patient remained alive within 5 y.…”

Section: Gpc3 Ihc Staining and Ctl Inductionmentioning

confidence: 96%

“…GPC3 IHC staining, CTL induction after vaccination, and plasma GPC3 were studied, as previously described. 47,52,53 Specimens were stained with hematoxylin and eosin or monoclonal antibodies (dilution 1:300) raised against GPC3 (clone 1G12; 1:200 dilution; BioMosaics) in accordance with the manufacturer's instructions. An ex vivo interferon-γ (IFN-γ) ELISPOT assay was performed in duplicate and PBMCs (5 × 10 5 /well) were treated with GPC3 peptide antigens to evaluate antigen-specific CTL responses.…”

Section: Sample Collection and Biomarker Analysismentioning

confidence: 99%

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Peptide vaccine as an adjuvant therapy for glypican‐3‐positive hepatocellular carcinoma induces peptide‐specific CTLs and improves long prognosis

et al. 2020

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There is no established postoperative adjuvant therapy for hepatocellular carcinoma (HCC), and improvement of patient prognosis has been limited. We conducted long‐term monitoring of patients within a phase II trial that targeted a cancer antigen, glypican‐3 (GPC3), specifically expressed in HCC. We sought to determine if the GPC3 peptide vaccine was an effective adjuvant therapy by monitoring disease‐free survival and overall survival. We also tracked GPC3 immunohistochemical (IHC) staining, CTL induction, and postoperative plasma GPC3 for a patient group that was administered the vaccine (n = 35) and an unvaccinated patient group that underwent surgery only (n = 33). The 1‐y recurrence rate after surgery was reduced by approximately 15%, and the 5‐y and 8‐y survival rates were improved by approximately 10% and 30%, respectively, in the vaccinated group compared with the unvaccinated group. Patients who were positive for GPC3 IHC staining were more likely to have induced CTLs, and 60% survived beyond 5 y. Vaccine efficacy had a positive relationship with plasma concentration of GPC3; high concentrations increased the 5‐y survival rate to 75%. We thus expect GPC3 vaccination in patients with HCC, who are positive for GPC3 IHC staining and/or plasma GPC3 to induce CTL and have significantly improved long‐term prognosis.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Gpc3 Ihc Staining and Ctl Inductionmentioning

confidence: 96%

Section: Sample Collection and Biomarker Analysismentioning

confidence: 99%

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Peptide vaccine as an adjuvant therapy for glypican‐3‐positive hepatocellular carcinoma induces peptide‐specific CTLs and improves long prognosis

et al. 2020

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“…In a chronically inflamed liver, HCV is thus likely to promote hepatic neoplasia by the growth of early CD81-negative neoplastic hepatocytes, which are resistant to HCV infection [ 128 ]. Given its upregulation in the blood of patients with HCV-associated HCC, GPC3 had been suggested as a biomarker [ 129 ].…”

Section: Signaling Pathways Associated With Candidate Serum Biomarmentioning

confidence: 99%

Profibrotic Signaling and HCC Risk during Chronic Viral Hepatitis: Biomarker Development

Virzì

González-Motos

Tavecchio

et al. 2021

JCM

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Despite breakthroughs in antiviral therapies, chronic viral hepatitis B and C are still the major causes of liver fibrosis and hepatocellular carcinoma (HCC). Importantly, even in patients with controlled infection or viral cure, the cancer risk cannot be fully eliminated, highlighting a persisting oncogenic pressure imposed by epigenetic imprinting and advanced liver disease. Reliable and minimally invasive biomarkers for early fibrosis and for residual HCC risk in HCV-cured patients are urgently needed. Chronic infection with HBV and/or HCV dysregulates oncogenic and profibrogenic signaling within the host, also displayed in the secretion of soluble factors to the blood. The study of virus-dysregulated signaling pathways may, therefore, contribute to the identification of reliable minimally invasive biomarkers for the detection of patients at early-stage liver disease potentially complementing existing noninvasive methods in clinics. With a focus on virus-induced signaling events, this review provides an overview of candidate blood biomarkers for liver disease and HCC risk associated with chronic viral hepatitis and epigenetic viral footprints.

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Circulating Proteoglycans/Glycosaminoglycans as Cancer Biomarkers

Lepedda

Nieddu

Karamanos

et al. 2022

Biology of Extracellular Matrix

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Plasma and tumoral glypican‐3 levels are correlated in patients with hepatitis C virus‐related hepatocellular carcinoma

Cited by 12 publications

References 45 publications

Peptide vaccine as an adjuvant therapy for glypican‐3‐positive hepatocellular carcinoma induces peptide‐specific CTLs and improves long prognosis

Peptide vaccine as an adjuvant therapy for glypican‐3‐positive hepatocellular carcinoma induces peptide‐specific CTLs and improves long prognosis

Profibrotic Signaling and HCC Risk during Chronic Viral Hepatitis: Biomarker Development

Circulating Proteoglycans/Glycosaminoglycans as Cancer Biomarkers

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