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dc.contributor.authorKhaliq, Ateeq M
dc.contributor.authorErdogan, Cihat
dc.contributor.authorKurt, Zeyneb
dc.contributor.authorTurgut, Sultan Sevgi
dc.contributor.authorGrunvald, Miles W
dc.contributor.authorRand, Tim
dc.contributor.authorKhare, Sonal
dc.contributor.authorBorgia, Jeffrey A
dc.contributor.authorHayden, Dana M
dc.contributor.authorPappas, Sam G
dc.contributor.authorGovekar, Henry R
dc.contributor.authorKam, Audrey E
dc.contributor.authorReiser, Jochen
dc.contributor.authorTuraga, Kiran
dc.contributor.authorRadovich, Milan
dc.contributor.authorZang, Yong
dc.contributor.authorQiu, Yingjie
dc.contributor.authorLiu, Yunlong
dc.contributor.authorFishel, Melissa L
dc.contributor.authorTurk, Anita
dc.contributor.authorGupta, Vineet
dc.contributor.authorAl-Sabti, Ram
dc.contributor.authorSubramanian, Janakiraman
dc.contributor.authorKuzel, Timothy M
dc.contributor.authorSadanandam, Anguraj
dc.contributor.authorWaldron, Levi
dc.contributor.authorHussain, Arif
dc.contributor.authorSaleem, Mohammad
dc.contributor.authorEl-Rayes, Bassel
dc.contributor.authorSalahudeen, Ameen A
dc.contributor.authorMasood, Ashiq
dc.date.accessioned2022-05-17T13:43:55Z
dc.date.available2022-05-17T13:43:55Z
dc.date.issued2022-05-11
dc.identifier.urihttp://hdl.handle.net/10713/18879
dc.descriptionFollowing publication of the original article [1], the authors noticed an error in Additional file 1. The incorrect Figure S5 was published. The corrected Additional file 1 is published in the correction and the original article [1] has been updated. See in https://doi.org/10.1186/s13059-022-02724-9.
dc.description.abstractBackground: Colorectal cancer (CRC) consensus molecular subtypes (CMS) have different immunological, stromal cell, and clinicopathological characteristics. Single-cell characterization of CMS subtype tumor microenvironments is required to elucidate mechanisms of tumor and stroma cell contributions to pathogenesis which may advance subtype-specific therapeutic development. We interrogate racially diverse human CRC samples and analyze multiple independent external cohorts for a total of 487,829 single cells enabling high-resolution depiction of the cellular diversity and heterogeneity within the tumor and microenvironmental cells. Results: Tumor cells recapitulate individual CMS subgroups yet exhibit significant intratumoral CMS heterogeneity. Both CMS1 microsatellite instability (MSI-H) CRCs and microsatellite stable (MSS) CRC demonstrate similar pathway activations at the tumor epithelial level. However, CD8+ cytotoxic T cell phenotype infiltration in MSI-H CRCs may explain why these tumors respond to immune checkpoint inhibitors. Cellular transcriptomic profiles in CRC exist in a tumor immune stromal continuum in contrast to discrete subtypes proposed by studies utilizing bulk transcriptomics. We note a dichotomy in tumor microenvironments across CMS subgroups exists by which patients with high cancer-associated fibroblasts (CAFs) and C1Q+TAM content exhibit poor outcomes, providing a higher level of personalization and precision than would distinct subtypes. Additionally, we discover CAF subtypes known to be associated with immunotherapy resistance. Conclusions: Distinct CAFs and C1Q+ TAMs are sufficient to explain CMS predictive ability and a simpler signature based on these cellular phenotypes could stratify CRC patient prognosis with greater precision. Therapeutically targeting specific CAF subtypes and C1Q + TAMs may promote immunotherapy responses in CRC patients.en_US
dc.description.urihttps://doi.org/10.1186/s13059-022-02677-zen_US
dc.description.urihttps://doi.org/10.1186/s13059-022-02724-9
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relationProcessed scRNA-seq and metadata are available in the NCBI Gene Expression Omnibus (GEO) database under the accession code GSE200997 [113]. Additionally, Seurat objects, matrix files are available on GitHub [43]. It is also been deposited to Zenodo (https://zenodo.org/) with assigned DOI: 10.5281/zenodo.6466249 [114]. Public datasets used in our analysis were downloaded from GEO under accession numbers GSE39582 [45], GSE17536 [48], GSE132465 [18], GSE144735 [18], and GSE178341 [19]; raw counts were directly obtained from the author [19], and scRNA-seq data from Kieffer et al. [28] was downloaded from Bioturing platform [21]. Due to privacy concerns for human patients, the raw FASTQ data used in this study will be made available upon request for scientific research.en_US
dc.relation.ispartofGenome Biologyen_US
dc.rights© 2022. The Author(s).en_US
dc.subjectCMS classificationen_US
dc.subjectCancer-associated fibroblasten_US
dc.subjectColorectal canceren_US
dc.subjectImmunotherapyen_US
dc.subjectSingle-cell analysisen_US
dc.subjectStromal signaturesen_US
dc.titleRefining colorectal cancer classification and clinical stratification through a single-cell atlas.en_US
dc.typeArticleen_US
dc.identifier.doi10.1186/s13059-022-02677-z
dc.identifier.pmid35538548
dc.source.journaltitleGenome biology
dc.source.volume23
dc.source.issue1
dc.source.beginpage113
dc.source.endpage
dc.source.countryEngland


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