Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer

Nakatsura, None

doi:10.3892/ijo_00000190

Cited by 36 publications

(8 citation statements)

References 44 publications

(54 reference statements)

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“…The HCC-selective target, glypican-3 (GPC3), is a known pathological marker of HCC and is overexpressed in approximately 75% of HCC [9][10][11][12]. GC33 (a.k.a.…”

Section: Introductionmentioning

confidence: 99%

Glypican-3-Targeted Alpha Particle Therapy for Hepatocellular Carcinoma

et al. 2020

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Glypican-3 (GPC3) is expressed in 75% of hepatocellular carcinoma (HCC), but not normal liver, making it a promising HCC therapeutic target. GC33 is a full-length humanized monoclonal IgG1 specific to GPC3 that can localize to HCC in vivo. GC33 alone failed to demonstrate therapeutic efficacy when evaluated in patients with HCC; however, we posit that cytotoxic functionalization of the antibody with therapeutic radionuclides, may be warranted. Alpha particles, which are emitted by radioisotopes such as Actinium-225 (Ac-225) exhibit high linear energy transfer and short pathlength that, when targeted to tumors, can effectively kill cancer and limit bystander cytotoxicity. Macropa, an 18-member heterocyclic crown ether, can stably chelate Ac-225 at room temperature. Here, we synthesized and evaluated the efficacy of [225Ac]Ac–Macropa–GC33 in mice engrafted with the GPC3-expressing human liver cancer cell line HepG2. Following a pilot dose-finding study, mice (n = 10 per group) were treated with (1) PBS, (2) mass-equivalent unmodified GC33, (3) 18.5 kBq [225Ac]Ac–Macropa–IgG1 (isotype control), (4) 9.25 kBq [225Ac]Ac–Macropa–GC33, and (5) 18.5 kBq [225Ac]Ac–Macropa–GC33. While significant toxicity was observed in all groups receiving radioconjugates, the 9.25 kBq [225Ac]Ac–Macropa–GC33 group demonstrated a modest survival advantage compared to PBS (p = 0.0012) and 18.5 kBq [225Ac]Ac–IgG1 (p = 0.0412). Hematological analysis demonstrated a marked, rapid reduction in white blood cells in all radioconjugate-treated groups compared to the PBS and unmodified GC33 control groups. Our studies highlight a significant disadvantage of using directly-labeled biomolecules with long blood circulation times for TAT. Strategies to mitigate such treatment toxicity include dose fractionation, pretargeting, and using smaller targeting ligands.

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“…The HCC-selective target, glypican-3 (GPC3), is a known pathological marker of HCC and is overexpressed in approximately 75% of HCC [9][10][11][12]. GC33 (a.k.a.…”

Section: Introductionmentioning

confidence: 99%

Glypican-3-Targeted Alpha Particle Therapy for Hepatocellular Carcinoma

et al. 2020

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“…High GPC3 expression levels in HCC may suggest poor differentiation, early metastasis, and poor prognosis [29] . A previous report showed that GPC3 immunostaining was positive in 78.3% (36/46) of HCCs and 72.7% (8/11) of the HCC components of CHC sections, yet negative in ICCs [30] . In our study, GPC3 immunostaining was positive in 79.2% (95/120) of HCCs and 82.4% (14/17) of CHCs, but few ICC (6/50), metastatic adenocarcinoma (2/20), and benign liver lesion (2/28) samples.…”

Section: Discussionmentioning

confidence: 82%

Immunohistochemical panel of glypican-3, hepatocyte paraffin antigen-1, arginase-1, cytokeratin-19, and human epithelial membrane antigen for the differential diagnosis of liver tumors*

朱冬灵

况东

邹思娟

et al. 2019

Oncology and Translational Medicine

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ObjectiveClinical immunohistochemistry plays an increasingly important role in pathologic diagnosis. We investigated the usefulness of an immunohistochemical panel of glypican-3 (GPC3), hepatocyte paraffin antigen-1 (HepPar-1), arginase-1 (Arg-1), cytokeratin-19 (CK19), and human epithelial membrane antigen (EMA) for the differential diagnosis of liver tumors.MethodsTwo hundred and thirty-five immunohistochemical sections of hepatocellular carcinoma (HCC; 120 cases), intrahepatic cholangiocarcinoma (ICC; 50 cases), combined hepatocellular and cholangiocarcinoma (CHC; 17 cases), metastatic adenocarcinoma (20 cases), and benign liver lesions(28 cases) were obtained from the Department of Pathology at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. The sensitivity and specificity of the combined biomarkers GPC3/HepPar-1/Arg-1/CK19/EMA for the differential diagnosis of HCC, ICC, and CHC were calculated and analyzed retrospectively.ResultsThe combined biomarkers GPC3+/CK19- had the highest specificity (98.3%) for diagnosing HCC, with a sensitivity of 60.0%. The specificity of GPC3-/HepPar-1-/Arg-1-/CK19+/EMA+ for diagnosing ICC was 93.0%, with a sensitivity of 76.0%. The specificity of GPC3+/HepPar-1+/Arg-1+/CK19+/EMA+ for diagnosing CHC was 95.9%, with a sensitivity of 52.9%.ConclusionThe combined biomarkers GPC3/HepPar-1/Arg-1/CK19/EMA greatly improved the specificity of liver tumor diagnosis. We believe that clinical pathological work could improve the original determination of liver nodules.

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“…It has been reported that cell-cycle regulators and cell division factors like BUB1, CDC25B, CDC45, CENPA, PRC1, PRIM1, RRM2, SPC24, and growth factor receptors like ADGRD1 and HMMR are up-regulated by the TSPY gene [ 102 ]. Shirakawa and colleagues showed the co-expression of TSPY and Glypican-3 ( GPC3 ) as a sensitive and specific biomarker of HCC [ 114 ]. Kido and colleagues identified a TSPY co-expression network (TCN) which activated in 30% of males with HCC [ 101 ].…”

Section: Liver Cancermentioning

confidence: 99%

Y chromosome is moving out of sex determination shadow

et al. 2022

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Although sex hormones play a key role in sex differences in susceptibility, severity, outcomes, and response to therapy of different diseases, sex chromosomes are also increasingly recognized as an important factor. Studies demonstrated that the Y chromosome is not a ‘genetic wasteland’ and can be a useful genetic marker for interpreting various male-specific physiological and pathophysiological characteristics. Y chromosome harbors male‑specific genes, which either solely or in cooperation with their X-counterpart, and independent or in conjunction with sex hormones have a considerable impact on basic physiology and disease mechanisms in most or all tissues development. Furthermore, loss of Y chromosome and/or aberrant expression of Y chromosome genes cause sex differences in disease mechanisms. With the launch of the human proteome project (HPP), the association of Y chromosome proteins with pathological conditions has been increasingly explored. In this review, the involvement of Y chromosome genes in male-specific diseases such as prostate cancer and the cases that are more prevalent in men, such as cardiovascular disease, neurological disease, and cancers, has been highlighted. Understanding the molecular mechanisms underlying Y chromosome-related diseases can have a significant impact on the prevention, diagnosis, and treatment of diseases.

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Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer

Cited by 36 publications

References 44 publications

Glypican-3-Targeted Alpha Particle Therapy for Hepatocellular Carcinoma

Glypican-3-Targeted Alpha Particle Therapy for Hepatocellular Carcinoma

Immunohistochemical panel of glypican-3, hepatocyte paraffin antigen-1, arginase-1, cytokeratin-19, and human epithelial membrane antigen for the differential diagnosis of liver tumors*

Y chromosome is moving out of sex determination shadow

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