Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer
Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape of liver cancer biospecimens from 19 patients. We found varying degrees of heterogeneity in malignant cells within and between...
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| Veröffentlicht in: | Cancer cell 2019-10, Vol.36 (4), p.418-430.e6 |
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| creator | Ma, Lichun Hernandez, Maria O. Zhao, Yongmei Mehta, Monika Tran, Bao Kelly, Michael Rae, Zachary Hernandez, Jonathan M. Davis, Jeremy L. Martin, Sean P. Kleiner, David E. Hewitt, Stephen M. Ylaya, Kris Wood, Bradford J. Greten, Tim F. Wang, Xin Wei |
| description | Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape of liver cancer biospecimens from 19 patients. We found varying degrees of heterogeneity in malignant cells within and between tumors and diverse landscapes of tumor microenvironment (TME). Strikingly, tumors with higher transcriptomic diversity were associated with patient's worse overall survival. We found a link between hypoxia-dependent vascular endothelial growth factor expression in tumor diversity and TME polarization. Moreover, T cells from higher heterogeneous tumors showed lower cytolytic activities. Consistent results were found using bulk genomic and transcriptomic profiles of 765 liver tumors. Our results offer insight into the diverse ecosystem of liver cancer and its impact on patient prognosis.
[Display omitted]
•HCC and iCCA have a varying degree of transcriptomic diversity•Tumor transcriptomic diversity is associated with patient outcomes•Tumor-derived VEGF drives microenvironmental reprogramming•T cells derived from higher heterogeneous tumors showed lower cytolytic activities
Ma et al. perform single-cell RNA sequencing of primary liver cancers and find heterogeneity in malignant cells and in the tumor microenvironment, the degree of which negatively associates with patient prognosis. They demonstrate that VEGF expression is linked to tumor diversity and T cell dysfunction. |
| doi_str_mv | 10.1016/j.ccell.2019.08.007 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6801104</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1535610819303757</els_id><sourcerecordid>31588021</sourcerecordid><originalsourceid>FETCH-LOGICAL-c459t-4667e7502f6e5f772ab4e7578ed1338a25260228dfe454e7747ae325ac0dca8a3</originalsourceid><addsrcrecordid>eNp9kNtKw0AQhhdRbK0-gSB5gcQ9ZA-9UNB4hEpB6vWy3UzqliRbNm2gb-_WquiNVzPDzP_PzIfQOcEZwURcLjNroa4zisk4wyrDWB6gIVFSpUwocRhzzngqCFYDdNJ1SxxVRI6P0YARrhSmZIims03jQ1JEo-TW-dL1EDq33iZ3IaZd8uJs8ND2Lvi2gXZt6uQVVsEvgmka1y4S1yaTnSgpTGshnKKjytQdnH3FEXp7uJ8VT-lk-vhc3ExSm_PxOs2FkCA5ppUAXklJzTyPtVRQEsaUoZwKTKkqK8h57MhcGmCUG4tLa5RhI3S9911t5g2UNp4WTK1XwTUmbLU3Tv_ttO5dL3yvhcKE4DwasL1B_K_rAlQ_WoL1jq9e6k--esdXY6Uj36i6-L32R_MNNA5c7QcgPt87CLqzDiKZ0gWwa1169--CD47ujxM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer</title><source>MEDLINE</source><source>Cell Press Archives</source><source>Elsevier ScienceDirect Journals Complete</source><source>EZB Electronic Journals Library</source><creator>Ma, Lichun ; Hernandez, Maria O. ; Zhao, Yongmei ; Mehta, Monika ; Tran, Bao ; Kelly, Michael ; Rae, Zachary ; Hernandez, Jonathan M. ; Davis, Jeremy L. ; Martin, Sean P. ; Kleiner, David E. ; Hewitt, Stephen M. ; Ylaya, Kris ; Wood, Bradford J. ; Greten, Tim F. ; Wang, Xin Wei</creator><creatorcontrib>Ma, Lichun ; Hernandez, Maria O. ; Zhao, Yongmei ; Mehta, Monika ; Tran, Bao ; Kelly, Michael ; Rae, Zachary ; Hernandez, Jonathan M. ; Davis, Jeremy L. ; Martin, Sean P. ; Kleiner, David E. ; Hewitt, Stephen M. ; Ylaya, Kris ; Wood, Bradford J. ; Greten, Tim F. ; Wang, Xin Wei</creatorcontrib><description>Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape of liver cancer biospecimens from 19 patients. We found varying degrees of heterogeneity in malignant cells within and between tumors and diverse landscapes of tumor microenvironment (TME). Strikingly, tumors with higher transcriptomic diversity were associated with patient's worse overall survival. We found a link between hypoxia-dependent vascular endothelial growth factor expression in tumor diversity and TME polarization. Moreover, T cells from higher heterogeneous tumors showed lower cytolytic activities. Consistent results were found using bulk genomic and transcriptomic profiles of 765 liver tumors. Our results offer insight into the diverse ecosystem of liver cancer and its impact on patient prognosis.
[Display omitted]
•HCC and iCCA have a varying degree of transcriptomic diversity•Tumor transcriptomic diversity is associated with patient outcomes•Tumor-derived VEGF drives microenvironmental reprogramming•T cells derived from higher heterogeneous tumors showed lower cytolytic activities
Ma et al. perform single-cell RNA sequencing of primary liver cancers and find heterogeneity in malignant cells and in the tumor microenvironment, the degree of which negatively associates with patient prognosis. They demonstrate that VEGF expression is linked to tumor diversity and T cell dysfunction.</description><identifier>ISSN: 1535-6108</identifier><identifier>EISSN: 1878-3686</identifier><identifier>DOI: 10.1016/j.ccell.2019.08.007</identifier><identifier>PMID: 31588021</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Immunological - pharmacology ; Antineoplastic Agents, Immunological - therapeutic use ; Bile Duct Neoplasms - genetics ; Bile Duct Neoplasms - mortality ; Bile Duct Neoplasms - pathology ; Bile Duct Neoplasms - therapy ; Bile Ducts, Intrahepatic - pathology ; Bile Ducts, Intrahepatic - surgery ; biodiversity ; Biopsy ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - mortality ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - therapy ; cholangiocarcinoma ; Cholangiocarcinoma - genetics ; Cholangiocarcinoma - mortality ; Cholangiocarcinoma - pathology ; Cholangiocarcinoma - therapy ; DNA Copy Number Variations ; Drug Resistance, Neoplasm - genetics ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Variation ; Hepatectomy ; hepatocellular carcinoma ; Humans ; Liver - pathology ; Liver - surgery ; liver cancer ; Liver Neoplasms - genetics ; Liver Neoplasms - mortality ; Liver Neoplasms - pathology ; Liver Neoplasms - therapy ; Male ; microenvironmental reprogramming ; Middle Aged ; Prognosis ; Progression-Free Survival ; RNA-Seq ; single-cell ; Single-Cell Analysis ; tumor ecosystem ; tumor heterogeneity ; Tumor Microenvironment - drug effects ; Tumor Microenvironment - genetics ; tumor microenvironments ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism ; VEGF</subject><ispartof>Cancer cell, 2019-10, Vol.36 (4), p.418-430.e6</ispartof><rights>2019</rights><rights>Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-4667e7502f6e5f772ab4e7578ed1338a25260228dfe454e7747ae325ac0dca8a3</citedby><cites>FETCH-LOGICAL-c459t-4667e7502f6e5f772ab4e7578ed1338a25260228dfe454e7747ae325ac0dca8a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1535610819303757$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31588021$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Lichun</creatorcontrib><creatorcontrib>Hernandez, Maria O.</creatorcontrib><creatorcontrib>Zhao, Yongmei</creatorcontrib><creatorcontrib>Mehta, Monika</creatorcontrib><creatorcontrib>Tran, Bao</creatorcontrib><creatorcontrib>Kelly, Michael</creatorcontrib><creatorcontrib>Rae, Zachary</creatorcontrib><creatorcontrib>Hernandez, Jonathan M.</creatorcontrib><creatorcontrib>Davis, Jeremy L.</creatorcontrib><creatorcontrib>Martin, Sean P.</creatorcontrib><creatorcontrib>Kleiner, David E.</creatorcontrib><creatorcontrib>Hewitt, Stephen M.</creatorcontrib><creatorcontrib>Ylaya, Kris</creatorcontrib><creatorcontrib>Wood, Bradford J.</creatorcontrib><creatorcontrib>Greten, Tim F.</creatorcontrib><creatorcontrib>Wang, Xin Wei</creatorcontrib><title>Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer</title><title>Cancer cell</title><addtitle>Cancer Cell</addtitle><description>Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape of liver cancer biospecimens from 19 patients. We found varying degrees of heterogeneity in malignant cells within and between tumors and diverse landscapes of tumor microenvironment (TME). Strikingly, tumors with higher transcriptomic diversity were associated with patient's worse overall survival. We found a link between hypoxia-dependent vascular endothelial growth factor expression in tumor diversity and TME polarization. Moreover, T cells from higher heterogeneous tumors showed lower cytolytic activities. Consistent results were found using bulk genomic and transcriptomic profiles of 765 liver tumors. Our results offer insight into the diverse ecosystem of liver cancer and its impact on patient prognosis.
[Display omitted]
•HCC and iCCA have a varying degree of transcriptomic diversity•Tumor transcriptomic diversity is associated with patient outcomes•Tumor-derived VEGF drives microenvironmental reprogramming•T cells derived from higher heterogeneous tumors showed lower cytolytic activities
Ma et al. perform single-cell RNA sequencing of primary liver cancers and find heterogeneity in malignant cells and in the tumor microenvironment, the degree of which negatively associates with patient prognosis. They demonstrate that VEGF expression is linked to tumor diversity and T cell dysfunction.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Agents, Immunological - pharmacology</subject><subject>Antineoplastic Agents, Immunological - therapeutic use</subject><subject>Bile Duct Neoplasms - genetics</subject><subject>Bile Duct Neoplasms - mortality</subject><subject>Bile Duct Neoplasms - pathology</subject><subject>Bile Duct Neoplasms - therapy</subject><subject>Bile Ducts, Intrahepatic - pathology</subject><subject>Bile Ducts, Intrahepatic - surgery</subject><subject>biodiversity</subject><subject>Biopsy</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - mortality</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - therapy</subject><subject>cholangiocarcinoma</subject><subject>Cholangiocarcinoma - genetics</subject><subject>Cholangiocarcinoma - mortality</subject><subject>Cholangiocarcinoma - pathology</subject><subject>Cholangiocarcinoma - therapy</subject><subject>DNA Copy Number Variations</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic Variation</subject><subject>Hepatectomy</subject><subject>hepatocellular carcinoma</subject><subject>Humans</subject><subject>Liver - pathology</subject><subject>Liver - surgery</subject><subject>liver cancer</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - mortality</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - therapy</subject><subject>Male</subject><subject>microenvironmental reprogramming</subject><subject>Middle Aged</subject><subject>Prognosis</subject><subject>Progression-Free Survival</subject><subject>RNA-Seq</subject><subject>single-cell</subject><subject>Single-Cell Analysis</subject><subject>tumor ecosystem</subject><subject>tumor heterogeneity</subject><subject>Tumor Microenvironment - drug effects</subject><subject>Tumor Microenvironment - genetics</subject><subject>tumor microenvironments</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>VEGF</subject><issn>1535-6108</issn><issn>1878-3686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kNtKw0AQhhdRbK0-gSB5gcQ9ZA-9UNB4hEpB6vWy3UzqliRbNm2gb-_WquiNVzPDzP_PzIfQOcEZwURcLjNroa4zisk4wyrDWB6gIVFSpUwocRhzzngqCFYDdNJ1SxxVRI6P0YARrhSmZIims03jQ1JEo-TW-dL1EDq33iZ3IaZd8uJs8ND2Lvi2gXZt6uQVVsEvgmka1y4S1yaTnSgpTGshnKKjytQdnH3FEXp7uJ8VT-lk-vhc3ExSm_PxOs2FkCA5ppUAXklJzTyPtVRQEsaUoZwKTKkqK8h57MhcGmCUG4tLa5RhI3S9911t5g2UNp4WTK1XwTUmbLU3Tv_ttO5dL3yvhcKE4DwasL1B_K_rAlQ_WoL1jq9e6k--esdXY6Uj36i6-L32R_MNNA5c7QcgPt87CLqzDiKZ0gWwa1169--CD47ujxM</recordid><startdate>20191014</startdate><enddate>20191014</enddate><creator>Ma, Lichun</creator><creator>Hernandez, Maria O.</creator><creator>Zhao, Yongmei</creator><creator>Mehta, Monika</creator><creator>Tran, Bao</creator><creator>Kelly, Michael</creator><creator>Rae, Zachary</creator><creator>Hernandez, Jonathan M.</creator><creator>Davis, Jeremy L.</creator><creator>Martin, Sean P.</creator><creator>Kleiner, David E.</creator><creator>Hewitt, Stephen M.</creator><creator>Ylaya, Kris</creator><creator>Wood, Bradford J.</creator><creator>Greten, Tim F.</creator><creator>Wang, Xin Wei</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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>5PM</scope></search><sort><creationdate>20191014</creationdate><title>Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer</title><author>Ma, Lichun ; Hernandez, Maria O. ; Zhao, Yongmei ; Mehta, Monika ; Tran, Bao ; Kelly, Michael ; Rae, Zachary ; Hernandez, Jonathan M. ; Davis, Jeremy L. ; Martin, Sean P. ; Kleiner, David E. ; Hewitt, Stephen M. ; Ylaya, Kris ; Wood, Bradford J. ; Greten, Tim F. ; Wang, Xin Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-4667e7502f6e5f772ab4e7578ed1338a25260228dfe454e7747ae325ac0dca8a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Agents, Immunological - pharmacology</topic><topic>Antineoplastic Agents, Immunological - therapeutic use</topic><topic>Bile Duct Neoplasms - genetics</topic><topic>Bile Duct Neoplasms - mortality</topic><topic>Bile Duct Neoplasms - pathology</topic><topic>Bile Duct Neoplasms - therapy</topic><topic>Bile Ducts, Intrahepatic - pathology</topic><topic>Bile Ducts, Intrahepatic - surgery</topic><topic>biodiversity</topic><topic>Biopsy</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - mortality</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - therapy</topic><topic>cholangiocarcinoma</topic><topic>Cholangiocarcinoma - genetics</topic><topic>Cholangiocarcinoma - mortality</topic><topic>Cholangiocarcinoma - pathology</topic><topic>Cholangiocarcinoma - therapy</topic><topic>DNA Copy Number Variations</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic Variation</topic><topic>Hepatectomy</topic><topic>hepatocellular carcinoma</topic><topic>Humans</topic><topic>Liver - pathology</topic><topic>Liver - surgery</topic><topic>liver cancer</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - mortality</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - therapy</topic><topic>Male</topic><topic>microenvironmental reprogramming</topic><topic>Middle Aged</topic><topic>Prognosis</topic><topic>Progression-Free Survival</topic><topic>RNA-Seq</topic><topic>single-cell</topic><topic>Single-Cell Analysis</topic><topic>tumor ecosystem</topic><topic>tumor heterogeneity</topic><topic>Tumor Microenvironment - drug effects</topic><topic>Tumor Microenvironment - genetics</topic><topic>tumor microenvironments</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>VEGF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Lichun</creatorcontrib><creatorcontrib>Hernandez, Maria O.</creatorcontrib><creatorcontrib>Zhao, Yongmei</creatorcontrib><creatorcontrib>Mehta, Monika</creatorcontrib><creatorcontrib>Tran, Bao</creatorcontrib><creatorcontrib>Kelly, Michael</creatorcontrib><creatorcontrib>Rae, Zachary</creatorcontrib><creatorcontrib>Hernandez, Jonathan M.</creatorcontrib><creatorcontrib>Davis, Jeremy L.</creatorcontrib><creatorcontrib>Martin, Sean P.</creatorcontrib><creatorcontrib>Kleiner, David E.</creatorcontrib><creatorcontrib>Hewitt, Stephen M.</creatorcontrib><creatorcontrib>Ylaya, Kris</creatorcontrib><creatorcontrib>Wood, Bradford J.</creatorcontrib><creatorcontrib>Greten, Tim F.</creatorcontrib><creatorcontrib>Wang, Xin Wei</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Lichun</au><au>Hernandez, Maria O.</au><au>Zhao, Yongmei</au><au>Mehta, Monika</au><au>Tran, Bao</au><au>Kelly, Michael</au><au>Rae, Zachary</au><au>Hernandez, Jonathan M.</au><au>Davis, Jeremy L.</au><au>Martin, Sean P.</au><au>Kleiner, David E.</au><au>Hewitt, Stephen M.</au><au>Ylaya, Kris</au><au>Wood, Bradford J.</au><au>Greten, Tim F.</au><au>Wang, Xin Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer</atitle><jtitle>Cancer cell</jtitle><addtitle>Cancer Cell</addtitle><date>2019-10-14</date><risdate>2019</risdate><volume>36</volume><issue>4</issue><spage>418</spage><epage>430.e6</epage><pages>418-430.e6</pages><issn>1535-6108</issn><eissn>1878-3686</eissn><abstract>Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape of liver cancer biospecimens from 19 patients. We found varying degrees of heterogeneity in malignant cells within and between tumors and diverse landscapes of tumor microenvironment (TME). Strikingly, tumors with higher transcriptomic diversity were associated with patient's worse overall survival. We found a link between hypoxia-dependent vascular endothelial growth factor expression in tumor diversity and TME polarization. Moreover, T cells from higher heterogeneous tumors showed lower cytolytic activities. Consistent results were found using bulk genomic and transcriptomic profiles of 765 liver tumors. Our results offer insight into the diverse ecosystem of liver cancer and its impact on patient prognosis.
[Display omitted]
•HCC and iCCA have a varying degree of transcriptomic diversity•Tumor transcriptomic diversity is associated with patient outcomes•Tumor-derived VEGF drives microenvironmental reprogramming•T cells derived from higher heterogeneous tumors showed lower cytolytic activities
Ma et al. perform single-cell RNA sequencing of primary liver cancers and find heterogeneity in malignant cells and in the tumor microenvironment, the degree of which negatively associates with patient prognosis. They demonstrate that VEGF expression is linked to tumor diversity and T cell dysfunction.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>31588021</pmid><doi>10.1016/j.ccell.2019.08.007</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Antineoplastic Agents, Immunological - pharmacology Antineoplastic Agents, Immunological - therapeutic use Bile Duct Neoplasms - genetics Bile Duct Neoplasms - mortality Bile Duct Neoplasms - pathology Bile Duct Neoplasms - therapy Bile Ducts, Intrahepatic - pathology Bile Ducts, Intrahepatic - surgery biodiversity Biopsy Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - mortality Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - therapy cholangiocarcinoma Cholangiocarcinoma - genetics Cholangiocarcinoma - mortality Cholangiocarcinoma - pathology Cholangiocarcinoma - therapy DNA Copy Number Variations Drug Resistance, Neoplasm - genetics Female Gene Expression Regulation, Neoplastic Genetic Variation Hepatectomy hepatocellular carcinoma Humans Liver - pathology Liver - surgery liver cancer Liver Neoplasms - genetics Liver Neoplasms - mortality Liver Neoplasms - pathology Liver Neoplasms - therapy Male microenvironmental reprogramming Middle Aged Prognosis Progression-Free Survival RNA-Seq single-cell Single-Cell Analysis tumor ecosystem tumor heterogeneity Tumor Microenvironment - drug effects Tumor Microenvironment - genetics tumor microenvironments Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - metabolism VEGF |
| title | Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer |
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