Integrated analysis of bulk and single‐cell RNA‐seq data reveals cell differentiation‐related subtypes and a scoring system in bladder cancer
Bladder cancer (BLCA) exhibits notable molecular heterogeneity, influencing diverse clinical outcomes. However, the molecular subtypes associated with cell differentiation‐related genes (CDR) and their prognostic implications remain unexplored. Analysing two GEO single‐cell datasets, we identified g...
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| Veröffentlicht in: | Journal of cellular and molecular medicine 2024-10, Vol.28 (19), p.e70111-n/a |
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| creator | Li, Sheng Zheng, Fucun Wang, Zhipeng Xiong, Situ Zeng, Jin Xu, Songhui Fu, Bin Liu, Xiaoqiang |
| description | Bladder cancer (BLCA) exhibits notable molecular heterogeneity, influencing diverse clinical outcomes. However, the molecular subtypes associated with cell differentiation‐related genes (CDR) and their prognostic implications remain unexplored. Analysing two GEO single‐cell datasets, we identified genes linked to cell differentiation. Utilizing these genes, we explored distinct molecular subtypes. WGCNA analysis further identified CDR‐associated genes, and the CDR score system, constructed using Lasso and Cox regression, was developed. Clinical prognosis and variations in immune‐related factors among patient groups were assessed. Core genes were selected and confirmed through in vitro experiments. Two BLCA subtypes related to cell differentiation were identified: Subtype B demonstrated a favourable prognosis, while Subtype A exhibited significant immune cell infiltration. The CDR score system of nine genes revealed a positive correlation between higher scores and a poorer prognosis. The comprehensive analysis uncovered a positive association between CDR genes and M2 macrophages and unresponsiveness to immune therapy. Functional experiments validated that ANXA5 downregulation influences tumour cell migration without affecting proliferation. Our study reveals distinct cell differentiation‐related molecular subtypes and introduces the CDR scoring system in BLCA. ANXA5 emerges as a potential therapeutic target, offering promising avenues for personalized treatment strategies. |
| doi_str_mv | 10.1111/jcmm.70111 |
| format | Article |
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However, the molecular subtypes associated with cell differentiation‐related genes (CDR) and their prognostic implications remain unexplored. Analysing two GEO single‐cell datasets, we identified genes linked to cell differentiation. Utilizing these genes, we explored distinct molecular subtypes. WGCNA analysis further identified CDR‐associated genes, and the CDR score system, constructed using Lasso and Cox regression, was developed. Clinical prognosis and variations in immune‐related factors among patient groups were assessed. Core genes were selected and confirmed through in vitro experiments. Two BLCA subtypes related to cell differentiation were identified: Subtype B demonstrated a favourable prognosis, while Subtype A exhibited significant immune cell infiltration. The CDR score system of nine genes revealed a positive correlation between higher scores and a poorer prognosis. The comprehensive analysis uncovered a positive association between CDR genes and M2 macrophages and unresponsiveness to immune therapy. Functional experiments validated that ANXA5 downregulation influences tumour cell migration without affecting proliferation. Our study reveals distinct cell differentiation‐related molecular subtypes and introduces the CDR scoring system in BLCA. ANXA5 emerges as a potential therapeutic target, offering promising avenues for personalized treatment strategies.</description><identifier>ISSN: 1582-1838</identifier><identifier>ISSN: 1582-4934</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.70111</identifier><identifier>PMID: 39400959</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Biomarkers, Tumor - genetics ; Bladder cancer ; Cell differentiation ; Cell Differentiation - genetics ; Cell Line, Tumor ; Cell Movement - genetics ; Cell Proliferation - genetics ; Cells ; Datasets ; Female ; Gene expression ; Gene Expression Profiling - methods ; Gene Expression Regulation, Neoplastic ; Humans ; Immunology ; Immunotherapy ; Leukocyte migration ; Macrophages ; Male ; Medical prognosis ; Metastases ; Original ; Prognosis ; RNA-Seq ; Single-Cell Analysis - methods ; Single-Cell Gene Expression Analysis ; single‐cell data ; subtypes ; Survival analysis ; Therapeutic targets ; Tumors ; Urinary Bladder Neoplasms - genetics ; Urinary Bladder Neoplasms - pathology ; WGCNA</subject><ispartof>Journal of cellular and molecular medicine, 2024-10, Vol.28 (19), p.e70111-n/a</ispartof><rights>2024 The Author(s). published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3381-64d0771e57e6836f3e834529a974d95bfb4de2fd222dcbfe6fcecbc53742181e3</cites><orcidid>0000-0001-5318-3873</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/PMC11481023/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481023/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39400959$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Sheng</creatorcontrib><creatorcontrib>Zheng, Fucun</creatorcontrib><creatorcontrib>Wang, Zhipeng</creatorcontrib><creatorcontrib>Xiong, Situ</creatorcontrib><creatorcontrib>Zeng, Jin</creatorcontrib><creatorcontrib>Xu, Songhui</creatorcontrib><creatorcontrib>Fu, Bin</creatorcontrib><creatorcontrib>Liu, Xiaoqiang</creatorcontrib><title>Integrated analysis of bulk and single‐cell RNA‐seq data reveals cell differentiation‐related subtypes and a scoring system in bladder cancer</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>Bladder cancer (BLCA) exhibits notable molecular heterogeneity, influencing diverse clinical outcomes. However, the molecular subtypes associated with cell differentiation‐related genes (CDR) and their prognostic implications remain unexplored. Analysing two GEO single‐cell datasets, we identified genes linked to cell differentiation. Utilizing these genes, we explored distinct molecular subtypes. WGCNA analysis further identified CDR‐associated genes, and the CDR score system, constructed using Lasso and Cox regression, was developed. Clinical prognosis and variations in immune‐related factors among patient groups were assessed. Core genes were selected and confirmed through in vitro experiments. Two BLCA subtypes related to cell differentiation were identified: Subtype B demonstrated a favourable prognosis, while Subtype A exhibited significant immune cell infiltration. The CDR score system of nine genes revealed a positive correlation between higher scores and a poorer prognosis. The comprehensive analysis uncovered a positive association between CDR genes and M2 macrophages and unresponsiveness to immune therapy. Functional experiments validated that ANXA5 downregulation influences tumour cell migration without affecting proliferation. Our study reveals distinct cell differentiation‐related molecular subtypes and introduces the CDR scoring system in BLCA. ANXA5 emerges as a potential therapeutic target, offering promising avenues for personalized treatment strategies.</description><subject>Biomarkers, Tumor - genetics</subject><subject>Bladder cancer</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>Cells</subject><subject>Datasets</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Leukocyte migration</subject><subject>Macrophages</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Original</subject><subject>Prognosis</subject><subject>RNA-Seq</subject><subject>Single-Cell Analysis - methods</subject><subject>Single-Cell Gene Expression Analysis</subject><subject>single‐cell data</subject><subject>subtypes</subject><subject>Survival analysis</subject><subject>Therapeutic targets</subject><subject>Tumors</subject><subject>Urinary Bladder Neoplasms - genetics</subject><subject>Urinary Bladder Neoplasms - pathology</subject><subject>WGCNA</subject><issn>1582-1838</issn><issn>1582-4934</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kd9qFDEUh4MotlZvfAAJeFMKW5NJ5k-upCzWVloF0euQSU7WrJnJNpmpzJ2PIPiGPkmzO2tRL8xNDud8fBzOD6HnlJzS_F6tdded1iSXD9AhLZtiwQXjD_c1bVhzgJ6ktCaEVZSJx-iACU6IKMUh-nnZD7CKagCDVa_8lFzCweJ29F9zw-Dk-pWHX99_aPAef3x_lssEN9ioQeEIt6B8wruZcdZChH5wanChz1wEvxOnsR2mDaSdUOGkQ8xWnKY0QIddj1uvjIGIteo1xKfokc1WeLb_j9Dn8zeflheLqw9vL5dnVwvNWEMXFTekrimUNVQNqyyDhvGyEErU3IiytS03UFhTFIXRrYXKatCtLlnNC9pQYEfo9ezdjG0HRufVo_JyE12n4iSDcvLvSe--yFW4lZTyhpKCZcPx3hDDzQhpkJ1L22OoHsKYJKO0YkyQps7oy3_QdRhjvvhM8VrQoszUyUzpGFKKYO-3oURuw5bbsOUu7Ay_-HP_e_R3uhmgM_DNeZj-o5LvltfXs_QO4UC6vg</recordid><startdate>202410</startdate><enddate>202410</enddate><creator>Li, Sheng</creator><creator>Zheng, Fucun</creator><creator>Wang, Zhipeng</creator><creator>Xiong, Situ</creator><creator>Zeng, Jin</creator><creator>Xu, Songhui</creator><creator>Fu, Bin</creator><creator>Liu, Xiaoqiang</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5318-3873</orcidid></search><sort><creationdate>202410</creationdate><title>Integrated analysis of bulk and single‐cell RNA‐seq data reveals cell differentiation‐related subtypes and a scoring system in bladder cancer</title><author>Li, Sheng ; Zheng, Fucun ; Wang, Zhipeng ; Xiong, Situ ; Zeng, Jin ; Xu, Songhui ; Fu, Bin ; Liu, Xiaoqiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3381-64d0771e57e6836f3e834529a974d95bfb4de2fd222dcbfe6fcecbc53742181e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Biomarkers, Tumor - genetics</topic><topic>Bladder cancer</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - genetics</topic><topic>Cell Proliferation - genetics</topic><topic>Cells</topic><topic>Datasets</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Immunology</topic><topic>Immunotherapy</topic><topic>Leukocyte migration</topic><topic>Macrophages</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Original</topic><topic>Prognosis</topic><topic>RNA-Seq</topic><topic>Single-Cell Analysis - methods</topic><topic>Single-Cell Gene Expression Analysis</topic><topic>single‐cell data</topic><topic>subtypes</topic><topic>Survival analysis</topic><topic>Therapeutic targets</topic><topic>Tumors</topic><topic>Urinary Bladder Neoplasms - genetics</topic><topic>Urinary Bladder Neoplasms - pathology</topic><topic>WGCNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Sheng</creatorcontrib><creatorcontrib>Zheng, Fucun</creatorcontrib><creatorcontrib>Wang, Zhipeng</creatorcontrib><creatorcontrib>Xiong, Situ</creatorcontrib><creatorcontrib>Zeng, Jin</creatorcontrib><creatorcontrib>Xu, Songhui</creatorcontrib><creatorcontrib>Fu, Bin</creatorcontrib><creatorcontrib>Liu, Xiaoqiang</creatorcontrib><collection>Wiley-Blackwell Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health Medical collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Science Journals</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Sheng</au><au>Zheng, Fucun</au><au>Wang, Zhipeng</au><au>Xiong, Situ</au><au>Zeng, Jin</au><au>Xu, Songhui</au><au>Fu, Bin</au><au>Liu, Xiaoqiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integrated analysis of bulk and single‐cell RNA‐seq data reveals cell differentiation‐related subtypes and a scoring system in bladder cancer</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2024-10</date><risdate>2024</risdate><volume>28</volume><issue>19</issue><spage>e70111</spage><epage>n/a</epage><pages>e70111-n/a</pages><issn>1582-1838</issn><issn>1582-4934</issn><eissn>1582-4934</eissn><abstract>Bladder cancer (BLCA) exhibits notable molecular heterogeneity, influencing diverse clinical outcomes. However, the molecular subtypes associated with cell differentiation‐related genes (CDR) and their prognostic implications remain unexplored. Analysing two GEO single‐cell datasets, we identified genes linked to cell differentiation. Utilizing these genes, we explored distinct molecular subtypes. WGCNA analysis further identified CDR‐associated genes, and the CDR score system, constructed using Lasso and Cox regression, was developed. Clinical prognosis and variations in immune‐related factors among patient groups were assessed. Core genes were selected and confirmed through in vitro experiments. Two BLCA subtypes related to cell differentiation were identified: Subtype B demonstrated a favourable prognosis, while Subtype A exhibited significant immune cell infiltration. The CDR score system of nine genes revealed a positive correlation between higher scores and a poorer prognosis. The comprehensive analysis uncovered a positive association between CDR genes and M2 macrophages and unresponsiveness to immune therapy. Functional experiments validated that ANXA5 downregulation influences tumour cell migration without affecting proliferation. Our study reveals distinct cell differentiation‐related molecular subtypes and introduces the CDR scoring system in BLCA. ANXA5 emerges as a potential therapeutic target, offering promising avenues for personalized treatment strategies.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>39400959</pmid><doi>10.1111/jcmm.70111</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-5318-3873</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Biomarkers, Tumor - genetics Bladder cancer Cell differentiation Cell Differentiation - genetics Cell Line, Tumor Cell Movement - genetics Cell Proliferation - genetics Cells Datasets Female Gene expression Gene Expression Profiling - methods Gene Expression Regulation, Neoplastic Humans Immunology Immunotherapy Leukocyte migration Macrophages Male Medical prognosis Metastases Original Prognosis RNA-Seq Single-Cell Analysis - methods Single-Cell Gene Expression Analysis single‐cell data subtypes Survival analysis Therapeutic targets Tumors Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - pathology WGCNA |
| title | Integrated analysis of bulk and single‐cell RNA‐seq data reveals cell differentiation‐related subtypes and a scoring system in bladder cancer |
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