Clinical Significance of Glycolytic Metabolic Activity in Hepatocellular Carcinoma
High metabolic activity is a hallmark of cancers, including hepatocellular carcinoma (HCC). However, the molecular features of HCC with high metabolic activity contributing to clinical outcomes and the therapeutic implications of these characteristics are poorly understood. We aimed to define the fe...
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| Veröffentlicht in: | Cancers 2022-12, Vol.15 (1), p.186 |
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| creator | Jung, Joann Park, Sowon Jang, Yeonwoo Lee, Sung-Hwan Jeong, Yun Seong Yim, Sun Young Lee, Ju-Seog |
| description | High metabolic activity is a hallmark of cancers, including hepatocellular carcinoma (HCC). However, the molecular features of HCC with high metabolic activity contributing to clinical outcomes and the therapeutic implications of these characteristics are poorly understood. We aimed to define the features of HCC with high metabolic activity and uncover its association with response to current therapies. By integrating gene expression data from mouse liver tissues and tumor tissues from HCC patients (
= 1038), we uncovered three metabolically distinct HCC subtypes that differ in clinical outcomes and underlying molecular biology. The high metabolic subtype is characterized by poor survival, the strongest stem cell signature, high genomic instability, activation of EPCAM and SALL4, and low potential for benefitting from immunotherapy. Interestingly, immune cell analysis showed that regulatory T cells (Tregs) are highly enriched in high metabolic HCC tumors, suggesting that high metabolic activity of cancer cells may trigger activation or infiltration of Tregs, leading to cancer cells' evasion of anti-cancer immune cells. In summary, we identified clinically and metabolically distinct subtypes of HCC, potential biomarkers associated with these subtypes, and a potential mechanism of metabolism-mediated immune evasion by HCC cells. |
| doi_str_mv | 10.3390/cancers15010186 |
| format | Article |
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= 1038), we uncovered three metabolically distinct HCC subtypes that differ in clinical outcomes and underlying molecular biology. The high metabolic subtype is characterized by poor survival, the strongest stem cell signature, high genomic instability, activation of EPCAM and SALL4, and low potential for benefitting from immunotherapy. Interestingly, immune cell analysis showed that regulatory T cells (Tregs) are highly enriched in high metabolic HCC tumors, suggesting that high metabolic activity of cancer cells may trigger activation or infiltration of Tregs, leading to cancer cells' evasion of anti-cancer immune cells. In summary, we identified clinically and metabolically distinct subtypes of HCC, potential biomarkers associated with these subtypes, and a potential mechanism of metabolism-mediated immune evasion by HCC cells.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers15010186</identifier><identifier>PMID: 36612182</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Cancer therapies ; Cell activation ; Cell growth ; Cell metabolism ; Cell survival ; Clinical significance ; Development and progression ; Drinking water ; Gene expression ; Genomes ; Genomic instability ; Genomics ; Glucose ; Glycolysis ; Health aspects ; Hepatocellular carcinoma ; Hepatoma ; Immunoregulation ; Immunotherapy ; Kinases ; Liver cancer ; Lymphocytes T ; Medical prognosis ; Metabolism ; Metastases ; Oxidative stress ; Stem cells ; Tumors</subject><ispartof>Cancers, 2022-12, Vol.15 (1), p.186</ispartof><rights>COPYRIGHT 2022 MDPI AG</rights><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-7ec0cdb4bace227c8d022951d7a5a1796bbbcf38c54f992f0e2be734513afca3</citedby><cites>FETCH-LOGICAL-c488t-7ec0cdb4bace227c8d022951d7a5a1796bbbcf38c54f992f0e2be734513afca3</cites><orcidid>0000-0002-5666-9753</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818850/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818850/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36612182$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jung, Joann</creatorcontrib><creatorcontrib>Park, Sowon</creatorcontrib><creatorcontrib>Jang, Yeonwoo</creatorcontrib><creatorcontrib>Lee, Sung-Hwan</creatorcontrib><creatorcontrib>Jeong, Yun Seong</creatorcontrib><creatorcontrib>Yim, Sun Young</creatorcontrib><creatorcontrib>Lee, Ju-Seog</creatorcontrib><title>Clinical Significance of Glycolytic Metabolic Activity in Hepatocellular Carcinoma</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>High metabolic activity is a hallmark of cancers, including hepatocellular carcinoma (HCC). However, the molecular features of HCC with high metabolic activity contributing to clinical outcomes and the therapeutic implications of these characteristics are poorly understood. We aimed to define the features of HCC with high metabolic activity and uncover its association with response to current therapies. By integrating gene expression data from mouse liver tissues and tumor tissues from HCC patients (
= 1038), we uncovered three metabolically distinct HCC subtypes that differ in clinical outcomes and underlying molecular biology. The high metabolic subtype is characterized by poor survival, the strongest stem cell signature, high genomic instability, activation of EPCAM and SALL4, and low potential for benefitting from immunotherapy. Interestingly, immune cell analysis showed that regulatory T cells (Tregs) are highly enriched in high metabolic HCC tumors, suggesting that high metabolic activity of cancer cells may trigger activation or infiltration of Tregs, leading to cancer cells' evasion of anti-cancer immune cells. In summary, we identified clinically and metabolically distinct subtypes of HCC, potential biomarkers associated with these subtypes, and a potential mechanism of metabolism-mediated immune evasion by HCC cells.</description><subject>Cancer therapies</subject><subject>Cell activation</subject><subject>Cell growth</subject><subject>Cell metabolism</subject><subject>Cell survival</subject><subject>Clinical significance</subject><subject>Development and progression</subject><subject>Drinking water</subject><subject>Gene expression</subject><subject>Genomes</subject><subject>Genomic instability</subject><subject>Genomics</subject><subject>Glucose</subject><subject>Glycolysis</subject><subject>Health aspects</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatoma</subject><subject>Immunoregulation</subject><subject>Immunotherapy</subject><subject>Kinases</subject><subject>Liver cancer</subject><subject>Lymphocytes T</subject><subject>Medical prognosis</subject><subject>Metabolism</subject><subject>Metastases</subject><subject>Oxidative stress</subject><subject>Stem cells</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkstr3DAQxkVoaEKac2_F0Esvm-hh63EpLEuaBFIKbe5CHksbBVnaSnZg__tq806odNAw-n3fMNIg9JngE8YUPgUTweZCOkwwkXwPHVIs6IJz1X54FR-g41JucV2MEcHFR3TAOCeUSHqIfq-Cjx5MaP74dfTO35s2yTXnYQspbCcPzU87mT6FGi1h8nd-2jY-Nhd2Y6YENoQ5mNysTAYf02g-oX1nQrHHj-cRuv5xdr26WFz9Or9cLa8W0Eo5LYQFDEPf9gYspQLkgClVHRmE6QwRivd9D45J6FqnFHXY0t4K1naEGQeGHaHvD7abuR_tADZO2QS9yX40eauT8frtTfQ3ep3utJJEyg5Xg2-PBjn9nW2Z9OjLrh0TbZqLpoITJURHVUW_vkNv05xj7e6eIhhTxl-otQlW--hSrQs7U70UbUcFo3RX9uQ_VN2DHT2kaJ2v-TeC0wcB5FRKtu65R4L1bhD0u0Goii-vn-aZf_p29g_3D6-_</recordid><startdate>20221228</startdate><enddate>20221228</enddate><creator>Jung, Joann</creator><creator>Park, Sowon</creator><creator>Jang, Yeonwoo</creator><creator>Lee, Sung-Hwan</creator><creator>Jeong, Yun Seong</creator><creator>Yim, Sun Young</creator><creator>Lee, Ju-Seog</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5666-9753</orcidid></search><sort><creationdate>20221228</creationdate><title>Clinical Significance of Glycolytic Metabolic Activity in Hepatocellular Carcinoma</title><author>Jung, Joann ; 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= 1038), we uncovered three metabolically distinct HCC subtypes that differ in clinical outcomes and underlying molecular biology. The high metabolic subtype is characterized by poor survival, the strongest stem cell signature, high genomic instability, activation of EPCAM and SALL4, and low potential for benefitting from immunotherapy. Interestingly, immune cell analysis showed that regulatory T cells (Tregs) are highly enriched in high metabolic HCC tumors, suggesting that high metabolic activity of cancer cells may trigger activation or infiltration of Tregs, leading to cancer cells' evasion of anti-cancer immune cells. In summary, we identified clinically and metabolically distinct subtypes of HCC, potential biomarkers associated with these subtypes, and a potential mechanism of metabolism-mediated immune evasion by HCC cells.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36612182</pmid><doi>10.3390/cancers15010186</doi><orcidid>https://orcid.org/0000-0002-5666-9753</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cancer therapies Cell activation Cell growth Cell metabolism Cell survival Clinical significance Development and progression Drinking water Gene expression Genomes Genomic instability Genomics Glucose Glycolysis Health aspects Hepatocellular carcinoma Hepatoma Immunoregulation Immunotherapy Kinases Liver cancer Lymphocytes T Medical prognosis Metabolism Metastases Oxidative stress Stem cells Tumors |
| title | Clinical Significance of Glycolytic Metabolic Activity in Hepatocellular Carcinoma |
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