{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:44:55Z","timestamp":1792820695324,"version":"4.5.0"},"reference-count":40,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":372,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012476","name":"Fundamental Research Funds for Central Universities of the Central South University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012476","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin City","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2020,7]]},"DOI":"10.1016\/j.ymthe.2020.04.023","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T02:25:28Z","timestamp":1588127128000},"page":"1658-1672","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":161,"title":["Single-Cell Transcriptome Analysis Reveals Intratumoral Heterogeneity in ccRCC, which Results in Different Clinical Outcomes"],"prefix":"10.1016","volume":"28","author":[{"given":"Junyi","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2020.04.023_bib1","first-page":"394","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.ymthe.2020.04.023_bib2","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/s41581-019-0131-x","article-title":"The adjuvant treatment of kidney cancer: a multidisciplinary outlook","volume":"15","author":"Porta","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"10.1016\/j.ymthe.2020.04.023_bib3","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.eururo.2019.05.041","article-title":"Safe use of immune checkpoint inhibitors in the multidisciplinary management of urological cancer: the European Association of Urology position in 2019","volume":"76","author":"Grimm","year":"2019","journal-title":"Eur. Urol."},{"key":"10.1016\/j.ymthe.2020.04.023_bib4","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/s41571-019-0209-1","article-title":"Towards individualized therapy for metastatic renal cell carcinoma","volume":"16","author":"Kotecha","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.ymthe.2020.04.023_bib5","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1126\/science.1254257","article-title":"Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma","volume":"344","author":"Patel","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2020.04.023_bib6","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nri.2017.76","article-title":"Single-cell RNA sequencing to explore immune cell heterogeneity","volume":"18","author":"Papalexi","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ymthe.2020.04.023_bib7","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrc2067","article-title":"The tumour microenvironment as a target for chemoprevention","volume":"7","author":"Albini","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.ymthe.2020.04.023_bib8","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nrclinonc.2016.217","article-title":"Tumour-associated macrophages as treatment targets in oncology","volume":"14","author":"Mantovani","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.ymthe.2020.04.023_bib9","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/jnci\/djx121","article-title":"Targeting the myofibroblastic cancer-associated fibroblast phenotype through inhibition of NOX4","volume":"110","author":"Hanley","year":"2018","journal-title":"J.\u00a0Natl. Cancer Inst."},{"key":"10.1016\/j.ymthe.2020.04.023_bib10","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1126\/science.aat1699","article-title":"Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors","volume":"361","author":"Young","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2020.04.023_bib11","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1038\/s41467-019-10861-2","article-title":"A single-nucleus RNA-sequencing pipeline to decipher the molecular anatomy and pathophysiology of human kidneys","volume":"10","author":"Lake","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2020.04.023_bib12","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1172\/JCI120855","article-title":"Hypoxia, angiogenesis, and metabolism in the hereditary kidney cancers","volume":"129","author":"Chappell","year":"2019","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.ymthe.2020.04.023_bib13","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.vetimm.2019.04.003","article-title":"Mucosal expression of S100A12 (calgranulin C) and S100A8\/A9 (calprotectin) and correlation with serum and fecal concentrations in dogs with chronic inflammatory enteropathy","volume":"211","author":"Heilmann","year":"2019","journal-title":"Vet. Immunol. Immunopathol."},{"key":"10.1016\/j.ymthe.2020.04.023_bib14","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1471-2172-10-18","article-title":"Identification of novel transcriptional regulators involved in macrophage differentiation and activation in U937 cells","volume":"10","author":"Baek","year":"2009","journal-title":"BMC Immunol."},{"key":"10.1016\/j.ymthe.2020.04.023_bib15","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/ni.3486","article-title":"The transcriptional repressor Hes1 attenuates inflammation by regulating transcription elongation","volume":"17","author":"Shang","year":"2016","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.ymthe.2020.04.023_bib16","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.cell.2018.11.010","article-title":"Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3","volume":"176","author":"Wang","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2020.04.023_bib17","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1182\/blood-2005-01-0428","article-title":"A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-\u03baB and enhanced IRF-3\/STAT1 activation)","volume":"107","author":"Biswas","year":"2006","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2020.04.023_bib18","doi-asserted-by":"crossref","first-page":"731023","DOI":"10.1155\/2013\/731023","article-title":"Interferon-regulatory factors determine macrophage phenotype polarization","volume":"2013","author":"G\u00fcnthner","year":"2013","journal-title":"Mediators Inflamm."},{"key":"10.1016\/j.ymthe.2020.04.023_bib19","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nri2634","article-title":"Transcriptional control of the inflammatory response","volume":"9","author":"Medzhitov","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ymthe.2020.04.023_bib20","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-019-1324-y","article-title":"TOX is a critical regulator of tumour-specific T\u00a0cell differentiation","volume":"571","author":"Scott","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2020.04.023_bib21","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.immuni.2015.01.006","article-title":"The transcription factor NFAT promotes exhaustion of activated CD8+ T\u00a0cells","volume":"42","author":"Martinez","year":"2015","journal-title":"Immunity"},{"key":"10.1016\/j.ymthe.2020.04.023_bib22","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/nri.2016.80","article-title":"Regulatory circuits of T\u00a0cell function in cancer","volume":"16","author":"Speiser","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ymthe.2020.04.023_bib23","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1158\/2159-8290.CD-14-1507","article-title":"HIF2\u03b1-dependent lipid storage promotes endoplasmic reticulum homeostasis in clear-cell renal cell carcinoma","volume":"5","author":"Qiu","year":"2015","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ymthe.2020.04.023_bib24","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s12944-017-0574-7","article-title":"Suppression of adipocyte differentiation and lipid accumulation by stearidonic acid (SDA) in 3T3-L1 cells","volume":"16","author":"Li","year":"2017","journal-title":"Lipids Health Dis."},{"key":"10.1016\/j.ymthe.2020.04.023_bib25","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/s41467-019-09116-x","article-title":"A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma","volume":"10","author":"Syafruddin","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2020.04.023_bib26","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1158\/2326-6066.CIR-18-0891","article-title":"Tumor cells hijack macrophage-produced complement C1q to promote tumor growth","volume":"7","author":"Roumenina","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"10.1016\/j.ymthe.2020.04.023_bib27","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1158\/2159-8290.CD-19-0094","article-title":"Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts","volume":"9","author":"Elyada","year":"2019","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ymthe.2020.04.023_bib28","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1038\/s41591-018-0096-5","article-title":"Phenotype molding of stromal cells in the lung tumor microenvironment","volume":"24","author":"Lambrechts","year":"2018","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2020.04.023_bib29","doi-asserted-by":"crossref","first-page":"e10966","DOI":"10.1371\/journal.pone.0010966","article-title":"Hypoxia activates the K-ras proto-oncogene to stimulate angiogenesis and inhibit apoptosis in colon cancer cells","volume":"5","author":"Zeng","year":"2010","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ymthe.2020.04.023_bib30","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1093\/bioinformatics\/btq170","article-title":"ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking","volume":"26","author":"Wilkerson","year":"2010","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ymthe.2020.04.023_bib31","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.canlet.2016.01.043","article-title":"Tumor microenvironment and therapeutic response","volume":"387","author":"Wu","year":"2017","journal-title":"Cancer Lett."},{"key":"10.1016\/j.ymthe.2020.04.023_bib32","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.ccell.2019.02.009","article-title":"Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers, and therapeutic targets","volume":"35","author":"Cassetta","year":"2019","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ymthe.2020.04.023_bib33","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2018.79.2648","article-title":"The immunobiology of kidney cancer","volume":"36","author":"Drake","year":"2018","journal-title":"J.\u00a0Clin. Oncol."},{"key":"10.1016\/j.ymthe.2020.04.023_bib34","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2020.04.023_bib35","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/nbt.4314","article-title":"Dimensionality reduction for visualizing single-cell data using UMAP","volume":"37","author":"Becht","year":"2019","journal-title":"Nat. Biotechnol."},{"issue":"D1","key":"10.1016\/j.ymthe.2020.04.023_bib36","doi-asserted-by":"crossref","first-page":"D721","DOI":"10.1093\/nar\/gky900","article-title":"CellMarker: a manually curated resource of cell markers in human and mouse","volume":"47","author":"Zhang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2020.04.023_bib37","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: single-cell regulatory network inference and clustering","volume":"14","author":"Aibar","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymthe.2020.04.023_bib38","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/nmeth.4402","article-title":"Reversed graph embedding resolves complex single-cell trajectories","volume":"14","author":"Qiu","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymthe.2020.04.023_bib39","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"10.1016\/j.ymthe.2020.04.023_bib40","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41586-018-0698-6","article-title":"Single-cell reconstruction of the early maternal-fetal interface in humans","volume":"563","author":"Vento-Tormo","year":"2018","journal-title":"Nature"}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001620302057?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001620302057?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T17:57:09Z","timestamp":1761501429000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001620302057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["S1525001620302057"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2020.04.023","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2020,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Single-Cell Transcriptome Analysis Reveals Intratumoral Heterogeneity in ccRCC, which Results in Different Clinical Outcomes","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2020.04.023","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}]}}