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FOXM1 and CHD4 expression is associated with chemoresistance in hepatoblastoma
Hepatoblastoma (HB) is the most common malignant liver tumor in childhood. Although pre-operative cisplatin (CDDP)-based chemotherapy is often used in cases of HB, about 20％ of HB patients exhibit resistance to CDDP. Forkhead box protein M1 (FOXM1) and chromo-domain-helicase-DNA-binding protein 4 (C...
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| Published in: | Pathology, research and practice research and practice, 2024-06, Vol.258, p.155348-155348, Article 155348 |
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| container_title | Pathology, research and practice |
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| creator | Hino, Yuko Kohashi, Kenichi Tamaki, Akihiko Kawakubo, Naonori Hamada, Hiroshi Fukuhara, Masahiro Shibui, Yuichi Tajiri, Tatsuro Oda, Yoshinao |
| description | Hepatoblastoma (HB) is the most common malignant liver tumor in childhood. Although pre-operative cisplatin (CDDP)-based chemotherapy is often used in cases of HB, about 20％ of HB patients exhibit resistance to CDDP. Forkhead box protein M1 (FOXM1) and chromo-domain-helicase-DNA-binding protein 4 (CHD4) have been associated with CDDP resistance in various tumors. We here analyzed the immunohistochemical expression of FOXM1 and CHD4 in HB specimens of 33 patients (mean age: 20 months) post-chemotherapy. The differentiation of specimens was assessed using the digital pathology software QuPath®, and then the relation between the FOXM1 or CHD4 expression and the differentiation and various other clinicopathological parameters was investigated. The histological type was epithelial in 19 cases (57.6%) and mixed epithelial and mesenchymal in 14 cases (42.4%). Nine cases had only a fetal component, 1 case had only an embryonal component, 22 cases had both fetal and embryonal components, and 1 case had no viable tumor. Both the FOXM1 and CHD4 immunoexpressions were found significantly more frequently in the embryonal than fetal components (p |
| doi_str_mv | 10.1016/j.prp.2024.155348 |
| format | article |
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•FOXM1 and CHD4 were more immunoexpressed in embryonal than fetal component in HB.•Our scoring system using QuPath® should accurately assess FOXM1 expression in HB.•FOXM1 expression may be useful in evaluating the effect to CDDP-based chemotherapy.</description><identifier>ISSN: 0344-0338</identifier><identifier>EISSN: 1618-0631</identifier><identifier>DOI: 10.1016/j.prp.2024.155348</identifier><identifier>PMID: 38761648</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Antineoplastic Agents - therapeutic use ; Biomarkers, Tumor - analysis ; Biomarkers, Tumor - metabolism ; Chemoresistance ; Child ; Child, Preschool ; Chromo-domain-helicase-DNA-binding protein 4 (CHD4) ; Cisplatin ; Cisplatin - therapeutic use ; Drug Resistance, Neoplasm ; Female ; Forkhead box protein M1 (FOXM1) ; Forkhead Box Protein M1 - metabolism ; Hepatoblastoma ; Hepatoblastoma - drug therapy ; Hepatoblastoma - metabolism ; Hepatoblastoma - pathology ; Humans ; Infant ; Liver Neoplasms - drug therapy ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Male ; Mi-2 Nucleosome Remodeling and Deacetylase Complex - metabolism</subject><ispartof>Pathology, research and practice, 2024-06, Vol.258, p.155348-155348, Article 155348</ispartof><rights>2024 Elsevier GmbH</rights><rights>Copyright © 2024 Elsevier GmbH. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c348t-77df0f3f379cecc32c4dc7498a26110e2dd7b77f80e80c6e797cda85f7d7aefb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38761648$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hino, Yuko</creatorcontrib><creatorcontrib>Kohashi, Kenichi</creatorcontrib><creatorcontrib>Tamaki, Akihiko</creatorcontrib><creatorcontrib>Kawakubo, Naonori</creatorcontrib><creatorcontrib>Hamada, Hiroshi</creatorcontrib><creatorcontrib>Fukuhara, Masahiro</creatorcontrib><creatorcontrib>Shibui, Yuichi</creatorcontrib><creatorcontrib>Tajiri, Tatsuro</creatorcontrib><creatorcontrib>Oda, Yoshinao</creatorcontrib><title>FOXM1 and CHD4 expression is associated with chemoresistance in hepatoblastoma</title><title>Pathology, research and practice</title><addtitle>Pathol Res Pract</addtitle><description>Hepatoblastoma (HB) is the most common malignant liver tumor in childhood. Although pre-operative cisplatin (CDDP)-based chemotherapy is often used in cases of HB, about 20％ of HB patients exhibit resistance to CDDP. Forkhead box protein M1 (FOXM1) and chromo-domain-helicase-DNA-binding protein 4 (CHD4) have been associated with CDDP resistance in various tumors. We here analyzed the immunohistochemical expression of FOXM1 and CHD4 in HB specimens of 33 patients (mean age: 20 months) post-chemotherapy. The differentiation of specimens was assessed using the digital pathology software QuPath®, and then the relation between the FOXM1 or CHD4 expression and the differentiation and various other clinicopathological parameters was investigated. The histological type was epithelial in 19 cases (57.6%) and mixed epithelial and mesenchymal in 14 cases (42.4%). Nine cases had only a fetal component, 1 case had only an embryonal component, 22 cases had both fetal and embryonal components, and 1 case had no viable tumor. Both the FOXM1 and CHD4 immunoexpressions were found significantly more frequently in the embryonal than fetal components (p<0.0001 and p<0.0001, respectively). Regarding chemotherapy efficacy, the alpha-fetoprotein (AFP) level after chemotherapy was correlated with both the imaging shrinkage rate (R=-0.52) and histological residual rate (the percentage of the viable tumors of HB after chemotherapy)(R=0.62). High FOXM1 score was correlated with a high-postoperative AFP value (p<0.01) and a low AFP attenuation rate (p<0.05), but the FOXM1 score was not correlated with the imaging shrinkage rate (p=0.4418) or histological residual rate (p=0.4418). High CHD4 score showed a nonsignificant trend toward correlation with high postoperative AFP value (p=0.0849) and was not significantly correlated with the other parameters. Collectively, our results showed that FOXM1 expression may be useful in evaluating the response to CDDP-based chemotherapeutic regimens. Accurate measurement of FOXM1 expression by our scoring system using QuPath® is important in cases with mixed HB components of various differentiation levels.
[Display omitted]
•FOXM1 and CHD4 were more immunoexpressed in embryonal than fetal component in HB.•Our scoring system using QuPath® should accurately assess FOXM1 expression in HB.•FOXM1 expression may be useful in evaluating the effect to CDDP-based chemotherapy.</description><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Chemoresistance</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chromo-domain-helicase-DNA-binding protein 4 (CHD4)</subject><subject>Cisplatin</subject><subject>Cisplatin - therapeutic use</subject><subject>Drug Resistance, Neoplasm</subject><subject>Female</subject><subject>Forkhead box protein M1 (FOXM1)</subject><subject>Forkhead Box Protein M1 - metabolism</subject><subject>Hepatoblastoma</subject><subject>Hepatoblastoma - drug therapy</subject><subject>Hepatoblastoma - metabolism</subject><subject>Hepatoblastoma - pathology</subject><subject>Humans</subject><subject>Infant</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Mi-2 Nucleosome Remodeling and Deacetylase Complex - metabolism</subject><issn>0344-0338</issn><issn>1618-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kD1PwzAQhi0EoqXwA1iQR5YEO3ZtV0yoUIoEdAGJzXLti-qqiYOd8vHvSZXCyHTS3XOv7h6EzinJKaHiap03sckLUvCcjseMqwM0pIKqjAhGD9GQMM4zwpgaoJOU1oQQSTg9RgOmpKCCqyF6ni3enig2tcPT-S3H8NVESMmHGvuETUrBetOCw5--XWG7gip0c59aU1vAvsYraEwblhuT2lCZU3RUmk2Cs30dodfZ3ct0nj0u7h-mN4-Z7a5sMyldSUpWMjmxYC0rLHdW8okyhaCUQOGcXEpZKgKKWAFyIq0zalxKJw2USzZCl31uE8P7FlKrK58sbDamhrBNmpGxEKIoCtGhtEdtDClFKHUTfWXit6ZE7zTqdddp9E6j7jV2Oxf7-O2yAve38eutA657ALonPzxEnayHTonzEWyrXfD_xP8Amk6DMw</recordid><startdate>202406</startdate><enddate>202406</enddate><creator>Hino, Yuko</creator><creator>Kohashi, Kenichi</creator><creator>Tamaki, Akihiko</creator><creator>Kawakubo, Naonori</creator><creator>Hamada, Hiroshi</creator><creator>Fukuhara, Masahiro</creator><creator>Shibui, Yuichi</creator><creator>Tajiri, Tatsuro</creator><creator>Oda, Yoshinao</creator><general>Elsevier GmbH</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202406</creationdate><title>FOXM1 and CHD4 expression is associated with chemoresistance in hepatoblastoma</title><author>Hino, Yuko ; Kohashi, Kenichi ; Tamaki, Akihiko ; Kawakubo, Naonori ; Hamada, Hiroshi ; Fukuhara, Masahiro ; Shibui, Yuichi ; Tajiri, Tatsuro ; Oda, Yoshinao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c348t-77df0f3f379cecc32c4dc7498a26110e2dd7b77f80e80c6e797cda85f7d7aefb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Chemoresistance</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chromo-domain-helicase-DNA-binding protein 4 (CHD4)</topic><topic>Cisplatin</topic><topic>Cisplatin - therapeutic use</topic><topic>Drug Resistance, Neoplasm</topic><topic>Female</topic><topic>Forkhead box protein M1 (FOXM1)</topic><topic>Forkhead Box Protein M1 - metabolism</topic><topic>Hepatoblastoma</topic><topic>Hepatoblastoma - drug therapy</topic><topic>Hepatoblastoma - metabolism</topic><topic>Hepatoblastoma - pathology</topic><topic>Humans</topic><topic>Infant</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>Mi-2 Nucleosome Remodeling and Deacetylase Complex - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hino, Yuko</creatorcontrib><creatorcontrib>Kohashi, Kenichi</creatorcontrib><creatorcontrib>Tamaki, Akihiko</creatorcontrib><creatorcontrib>Kawakubo, Naonori</creatorcontrib><creatorcontrib>Hamada, Hiroshi</creatorcontrib><creatorcontrib>Fukuhara, Masahiro</creatorcontrib><creatorcontrib>Shibui, Yuichi</creatorcontrib><creatorcontrib>Tajiri, Tatsuro</creatorcontrib><creatorcontrib>Oda, Yoshinao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pathology, research and practice</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hino, Yuko</au><au>Kohashi, Kenichi</au><au>Tamaki, Akihiko</au><au>Kawakubo, Naonori</au><au>Hamada, Hiroshi</au><au>Fukuhara, Masahiro</au><au>Shibui, Yuichi</au><au>Tajiri, Tatsuro</au><au>Oda, Yoshinao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FOXM1 and CHD4 expression is associated with chemoresistance in hepatoblastoma</atitle><jtitle>Pathology, research and practice</jtitle><addtitle>Pathol Res Pract</addtitle><date>2024-06</date><risdate>2024</risdate><volume>258</volume><spage>155348</spage><epage>155348</epage><pages>155348-155348</pages><artnum>155348</artnum><issn>0344-0338</issn><eissn>1618-0631</eissn><abstract>Hepatoblastoma (HB) is the most common malignant liver tumor in childhood. Although pre-operative cisplatin (CDDP)-based chemotherapy is often used in cases of HB, about 20％ of HB patients exhibit resistance to CDDP. Forkhead box protein M1 (FOXM1) and chromo-domain-helicase-DNA-binding protein 4 (CHD4) have been associated with CDDP resistance in various tumors. We here analyzed the immunohistochemical expression of FOXM1 and CHD4 in HB specimens of 33 patients (mean age: 20 months) post-chemotherapy. The differentiation of specimens was assessed using the digital pathology software QuPath®, and then the relation between the FOXM1 or CHD4 expression and the differentiation and various other clinicopathological parameters was investigated. The histological type was epithelial in 19 cases (57.6%) and mixed epithelial and mesenchymal in 14 cases (42.4%). Nine cases had only a fetal component, 1 case had only an embryonal component, 22 cases had both fetal and embryonal components, and 1 case had no viable tumor. Both the FOXM1 and CHD4 immunoexpressions were found significantly more frequently in the embryonal than fetal components (p<0.0001 and p<0.0001, respectively). Regarding chemotherapy efficacy, the alpha-fetoprotein (AFP) level after chemotherapy was correlated with both the imaging shrinkage rate (R=-0.52) and histological residual rate (the percentage of the viable tumors of HB after chemotherapy)(R=0.62). High FOXM1 score was correlated with a high-postoperative AFP value (p<0.01) and a low AFP attenuation rate (p<0.05), but the FOXM1 score was not correlated with the imaging shrinkage rate (p=0.4418) or histological residual rate (p=0.4418). High CHD4 score showed a nonsignificant trend toward correlation with high postoperative AFP value (p=0.0849) and was not significantly correlated with the other parameters. Collectively, our results showed that FOXM1 expression may be useful in evaluating the response to CDDP-based chemotherapeutic regimens. Accurate measurement of FOXM1 expression by our scoring system using QuPath® is important in cases with mixed HB components of various differentiation levels.
[Display omitted]
•FOXM1 and CHD4 were more immunoexpressed in embryonal than fetal component in HB.•Our scoring system using QuPath® should accurately assess FOXM1 expression in HB.•FOXM1 expression may be useful in evaluating the effect to CDDP-based chemotherapy.</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>38761648</pmid><doi>10.1016/j.prp.2024.155348</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antineoplastic Agents - therapeutic use Biomarkers, Tumor - analysis Biomarkers, Tumor - metabolism Chemoresistance Child Child, Preschool Chromo-domain-helicase-DNA-binding protein 4 (CHD4) Cisplatin Cisplatin - therapeutic use Drug Resistance, Neoplasm Female Forkhead box protein M1 (FOXM1) Forkhead Box Protein M1 - metabolism Hepatoblastoma Hepatoblastoma - drug therapy Hepatoblastoma - metabolism Hepatoblastoma - pathology Humans Infant Liver Neoplasms - drug therapy Liver Neoplasms - metabolism Liver Neoplasms - pathology Male Mi-2 Nucleosome Remodeling and Deacetylase Complex - metabolism |
| title | FOXM1 and CHD4 expression is associated with chemoresistance in hepatoblastoma |
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