A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes
Simple Summary Bladder cancer (BC) development is highly related to immune cell infiltration. In this study, we aimed to construct a new classification of bladder cancer molecular subtypes based on immune-cell-associated CpG(Methylation) sites. The classification was accurate and stable. BC patients...
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| Veröffentlicht in: | Cancers 2020-10, Vol.12 (10), p.3054, Article 3054 |
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Bladder cancer (BC) development is highly related to immune cell infiltration. In this study, we aimed to construct a new classification of bladder cancer molecular subtypes based on immune-cell-associated CpG(Methylation) sites. The classification was accurate and stable. BC patients were successfully divided into three subtypes based on the immune-cell-associated CpG sites. The clinicopathologic features, distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN_respons, Type II IFN response, and DNA stemness score (DNAss) presented significant differences among the three subgroups. The specific genomic alteration was also different across subgroups. High-level immune infiltration showed a correlation with high-level methylation. A lower RNA stemness score (RNAss) was associated with higher immune infiltration. Cluster 2 demonstrated a better response to chemotherapy. The anti-cancer targeted drug therapy results are different among the three subgroups.
Background: Bladder cancer is highly related to immune cell infiltration. This study aimed to develop a new classification of BC molecular subtypes based on immune-cell-associated CpG sites. Methods: The genes of 28 types of immune cells were obtained from previous studies. Then, methylation sites corresponding to immune-cell-associated genes were acquired. Differentially methylated sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylated sites was performed to divide the sites into several subtypes. Then, the potential mechanism of different subtypes was explored. Results: Bladder cancer patients were divided into three groups. The cluster 3 subtype had the best prognosis. Cluster 1 had the poorest prognosis. The distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN Response, Type II IFN Response, and DNAss presented significant differences among the three subgroups. The distribution of genomic alterations was also different. Conclusions: The proposed classification was accurate and stable. BC patients could be divided into three subtypes based on the immune-cell-associated CpG sites. Specific biological signaling pathways, immune mechanis |
| doi_str_mv | 10.3390/cancers12103054 |
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| fullrecord | <record><control><sourceid>gale_webof</sourceid><recordid>TN_cdi_gale_infotracmisc_A642768920</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A642768920</galeid><sourcerecordid>A642768920</sourcerecordid><originalsourceid>FETCH-LOGICAL-c426t-4d8df10b46995fe50ba36f57b84e788a3692e27c87dfa5f27d23124daa6910d73</originalsourceid><addsrcrecordid>eNqNUUtrFTEUHkSxpXbtdsCNIGPzTmYj3A5aCy2i6DpkkpM2ZSapyYzSf2_uvaXarswmOfkeJydf07zG6D2lPTqxJlrIBROMKOLsWXNIkCSdED17_s_5oDku5QbVRSmWQr5sDihFPUGKHjZfN-0lLNd3k1lCit2pKeDab2AnU0rwwe6u2-Tb08k4B7kddk3bPbFC5_O8RmgHmKb2DCKUV80Lb6YCx_f7UfPj08fvw-fu4svZ-bC56CwjYumYU85jNDLR99wDR6OhwnM5KgZSqVr0BIi0SjpvuCfSEYoJc8aIHiMn6VHzYe97u44zOAtxyWbStznMJt_pZIJ-jMRwra_SLy15T3tCqsHbe4Ocfq5QFj2HYuscJkJaiyaMM8w5VrhS3zyh3qQ1xzqeJpxJThki6i_rykygQ_Sp9rVbU70RjEih6qdX1smeZXMqJYN_eDJGepurfpJrVai94jeMyRcboOIPqporVwxLzrcR4yEsu8yGtMalSt_9v5T-AY-HtBk</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2547534028</pqid></control><display><type>article</type><title>A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Luo, Qizhan ; Vogeli, Thomas-Alexander</creator><creatorcontrib>Luo, Qizhan ; Vogeli, Thomas-Alexander</creatorcontrib><description>Simple Summary
Bladder cancer (BC) development is highly related to immune cell infiltration. In this study, we aimed to construct a new classification of bladder cancer molecular subtypes based on immune-cell-associated CpG(Methylation) sites. The classification was accurate and stable. BC patients were successfully divided into three subtypes based on the immune-cell-associated CpG sites. The clinicopathologic features, distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN_respons, Type II IFN response, and DNA stemness score (DNAss) presented significant differences among the three subgroups. The specific genomic alteration was also different across subgroups. High-level immune infiltration showed a correlation with high-level methylation. A lower RNA stemness score (RNAss) was associated with higher immune infiltration. Cluster 2 demonstrated a better response to chemotherapy. The anti-cancer targeted drug therapy results are different among the three subgroups.
Background: Bladder cancer is highly related to immune cell infiltration. This study aimed to develop a new classification of BC molecular subtypes based on immune-cell-associated CpG sites. Methods: The genes of 28 types of immune cells were obtained from previous studies. Then, methylation sites corresponding to immune-cell-associated genes were acquired. Differentially methylated sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylated sites was performed to divide the sites into several subtypes. Then, the potential mechanism of different subtypes was explored. Results: Bladder cancer patients were divided into three groups. The cluster 3 subtype had the best prognosis. Cluster 1 had the poorest prognosis. The distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN Response, Type II IFN Response, and DNAss presented significant differences among the three subgroups. The distribution of genomic alterations was also different. Conclusions: The proposed classification was accurate and stable. BC patients could be divided into three subtypes based on the immune-cell-associated CpG sites. Specific biological signaling pathways, immune mechanisms, and genomic alterations were varied among the three subgroups. High-level immune infiltration was correlated with high-level methylation. The lower RNAss was associated with higher immune infiltration. The study of the intratumoral immune microenvironment may provide a new perspective for BC therapy.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers12103054</identifier><identifier>PMID: 33092083</identifier><language>eng</language><publisher>BASEL: Mdpi</publisher><subject>Adenomatous polyposis coli ; Biomarkers ; Bladder cancer ; Cancer ; Cancer therapies ; Chemotherapy ; Classification ; CpG islands ; Diagnosis ; DNA methylation ; Drug therapy ; FDA approval ; Gene expression ; Genetic aspects ; Genomics ; Health aspects ; Histocompatibility antigen HLA ; Immune system ; Immunotherapy ; Infiltration ; Interferon ; Life Sciences & Biomedicine ; Major histocompatibility complex ; Medical prognosis ; Metastases ; Metastasis ; Methylation ; Microenvironments ; Mutation ; Oncology ; Principal components analysis ; Prognosis ; Reclassification ; Science & Technology ; Tumors ; Vaccines</subject><ispartof>Cancers, 2020-10, Vol.12 (10), p.3054, Article 3054</ispartof><rights>COPYRIGHT 2020 MDPI AG</rights><rights>2020 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 (http://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>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>26</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000584175500001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c426t-4d8df10b46995fe50ba36f57b84e788a3692e27c87dfa5f27d23124daa6910d73</citedby><cites>FETCH-LOGICAL-c426t-4d8df10b46995fe50ba36f57b84e788a3692e27c87dfa5f27d23124daa6910d73</cites><orcidid>0000-0002-9390-9138</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/PMC7593922/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593922/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids></links><search><creatorcontrib>Luo, Qizhan</creatorcontrib><creatorcontrib>Vogeli, Thomas-Alexander</creatorcontrib><title>A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes</title><title>Cancers</title><addtitle>CANCERS</addtitle><description>Simple Summary
Bladder cancer (BC) development is highly related to immune cell infiltration. In this study, we aimed to construct a new classification of bladder cancer molecular subtypes based on immune-cell-associated CpG(Methylation) sites. The classification was accurate and stable. BC patients were successfully divided into three subtypes based on the immune-cell-associated CpG sites. The clinicopathologic features, distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN_respons, Type II IFN response, and DNA stemness score (DNAss) presented significant differences among the three subgroups. The specific genomic alteration was also different across subgroups. High-level immune infiltration showed a correlation with high-level methylation. A lower RNA stemness score (RNAss) was associated with higher immune infiltration. Cluster 2 demonstrated a better response to chemotherapy. The anti-cancer targeted drug therapy results are different among the three subgroups.
Background: Bladder cancer is highly related to immune cell infiltration. This study aimed to develop a new classification of BC molecular subtypes based on immune-cell-associated CpG sites. Methods: The genes of 28 types of immune cells were obtained from previous studies. Then, methylation sites corresponding to immune-cell-associated genes were acquired. Differentially methylated sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylated sites was performed to divide the sites into several subtypes. Then, the potential mechanism of different subtypes was explored. Results: Bladder cancer patients were divided into three groups. The cluster 3 subtype had the best prognosis. Cluster 1 had the poorest prognosis. The distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN Response, Type II IFN Response, and DNAss presented significant differences among the three subgroups. The distribution of genomic alterations was also different. Conclusions: The proposed classification was accurate and stable. BC patients could be divided into three subtypes based on the immune-cell-associated CpG sites. Specific biological signaling pathways, immune mechanisms, and genomic alterations were varied among the three subgroups. High-level immune infiltration was correlated with high-level methylation. The lower RNAss was associated with higher immune infiltration. The study of the intratumoral immune microenvironment may provide a new perspective for BC therapy.</description><subject>Adenomatous polyposis coli</subject><subject>Biomarkers</subject><subject>Bladder cancer</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Classification</subject><subject>CpG islands</subject><subject>Diagnosis</subject><subject>DNA methylation</subject><subject>Drug therapy</subject><subject>FDA approval</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genomics</subject><subject>Health aspects</subject><subject>Histocompatibility antigen HLA</subject><subject>Immune system</subject><subject>Immunotherapy</subject><subject>Infiltration</subject><subject>Interferon</subject><subject>Life Sciences & Biomedicine</subject><subject>Major histocompatibility complex</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Methylation</subject><subject>Microenvironments</subject><subject>Mutation</subject><subject>Oncology</subject><subject>Principal components analysis</subject><subject>Prognosis</subject><subject>Reclassification</subject><subject>Science & Technology</subject><subject>Tumors</subject><subject>Vaccines</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNUUtrFTEUHkSxpXbtdsCNIGPzTmYj3A5aCy2i6DpkkpM2ZSapyYzSf2_uvaXarswmOfkeJydf07zG6D2lPTqxJlrIBROMKOLsWXNIkCSdED17_s_5oDku5QbVRSmWQr5sDihFPUGKHjZfN-0lLNd3k1lCit2pKeDab2AnU0rwwe6u2-Tb08k4B7kddk3bPbFC5_O8RmgHmKb2DCKUV80Lb6YCx_f7UfPj08fvw-fu4svZ-bC56CwjYumYU85jNDLR99wDR6OhwnM5KgZSqVr0BIi0SjpvuCfSEYoJc8aIHiMn6VHzYe97u44zOAtxyWbStznMJt_pZIJ-jMRwra_SLy15T3tCqsHbe4Ocfq5QFj2HYuscJkJaiyaMM8w5VrhS3zyh3qQ1xzqeJpxJThki6i_rykygQ_Sp9rVbU70RjEih6qdX1smeZXMqJYN_eDJGepurfpJrVai94jeMyRcboOIPqporVwxLzrcR4yEsu8yGtMalSt_9v5T-AY-HtBk</recordid><startdate>20201020</startdate><enddate>20201020</enddate><creator>Luo, Qizhan</creator><creator>Vogeli, Thomas-Alexander</creator><general>Mdpi</general><general>MDPI AG</general><general>MDPI</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</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/0000-0002-9390-9138</orcidid></search><sort><creationdate>20201020</creationdate><title>A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes</title><author>Luo, Qizhan ; Vogeli, Thomas-Alexander</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-4d8df10b46995fe50ba36f57b84e788a3692e27c87dfa5f27d23124daa6910d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenomatous polyposis coli</topic><topic>Biomarkers</topic><topic>Bladder cancer</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Classification</topic><topic>CpG islands</topic><topic>Diagnosis</topic><topic>DNA methylation</topic><topic>Drug therapy</topic><topic>FDA approval</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Genomics</topic><topic>Health aspects</topic><topic>Histocompatibility antigen HLA</topic><topic>Immune system</topic><topic>Immunotherapy</topic><topic>Infiltration</topic><topic>Interferon</topic><topic>Life Sciences & Biomedicine</topic><topic>Major histocompatibility complex</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Methylation</topic><topic>Microenvironments</topic><topic>Mutation</topic><topic>Oncology</topic><topic>Principal components analysis</topic><topic>Prognosis</topic><topic>Reclassification</topic><topic>Science & Technology</topic><topic>Tumors</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luo, Qizhan</creatorcontrib><creatorcontrib>Vogeli, Thomas-Alexander</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luo, Qizhan</au><au>Vogeli, Thomas-Alexander</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes</atitle><jtitle>Cancers</jtitle><stitle>CANCERS</stitle><date>2020-10-20</date><risdate>2020</risdate><volume>12</volume><issue>10</issue><spage>3054</spage><pages>3054-</pages><artnum>3054</artnum><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Simple Summary
Bladder cancer (BC) development is highly related to immune cell infiltration. In this study, we aimed to construct a new classification of bladder cancer molecular subtypes based on immune-cell-associated CpG(Methylation) sites. The classification was accurate and stable. BC patients were successfully divided into three subtypes based on the immune-cell-associated CpG sites. The clinicopathologic features, distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN_respons, Type II IFN response, and DNA stemness score (DNAss) presented significant differences among the three subgroups. The specific genomic alteration was also different across subgroups. High-level immune infiltration showed a correlation with high-level methylation. A lower RNA stemness score (RNAss) was associated with higher immune infiltration. Cluster 2 demonstrated a better response to chemotherapy. The anti-cancer targeted drug therapy results are different among the three subgroups.
Background: Bladder cancer is highly related to immune cell infiltration. This study aimed to develop a new classification of BC molecular subtypes based on immune-cell-associated CpG sites. Methods: The genes of 28 types of immune cells were obtained from previous studies. Then, methylation sites corresponding to immune-cell-associated genes were acquired. Differentially methylated sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylated sites was performed to divide the sites into several subtypes. Then, the potential mechanism of different subtypes was explored. Results: Bladder cancer patients were divided into three groups. The cluster 3 subtype had the best prognosis. Cluster 1 had the poorest prognosis. The distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN Response, Type II IFN Response, and DNAss presented significant differences among the three subgroups. The distribution of genomic alterations was also different. Conclusions: The proposed classification was accurate and stable. BC patients could be divided into three subtypes based on the immune-cell-associated CpG sites. Specific biological signaling pathways, immune mechanisms, and genomic alterations were varied among the three subgroups. High-level immune infiltration was correlated with high-level methylation. The lower RNAss was associated with higher immune infiltration. The study of the intratumoral immune microenvironment may provide a new perspective for BC therapy.</abstract><cop>BASEL</cop><pub>Mdpi</pub><pmid>33092083</pmid><doi>10.3390/cancers12103054</doi><tpages>21</tpages><orcidid>https://orcid.org/0000-0002-9390-9138</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adenomatous polyposis coli Biomarkers Bladder cancer Cancer Cancer therapies Chemotherapy Classification CpG islands Diagnosis DNA methylation Drug therapy FDA approval Gene expression Genetic aspects Genomics Health aspects Histocompatibility antigen HLA Immune system Immunotherapy Infiltration Interferon Life Sciences & Biomedicine Major histocompatibility complex Medical prognosis Metastases Metastasis Methylation Microenvironments Mutation Oncology Principal components analysis Prognosis Reclassification Science & Technology Tumors Vaccines |
| title | A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes |
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