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Article: Comprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma

TitleComprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma
Authors
Issue Date2021
PublisherNature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html
Citation
Nature Communications, 2021, v. 12 n. 1, p. article no. 1540 How to Cite?
AbstractThe tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME.
Persistent Identifierhttp://hdl.handle.net/10722/300588
ISSN
2023 Impact Factor: 14.7
2023 SCImago Journal Rankings: 4.887
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGong, L-
dc.contributor.authorKwong, DLW-
dc.contributor.authorDai, W-
dc.contributor.authorWu, P-
dc.contributor.authorLi, S-
dc.contributor.authorYan, Q-
dc.contributor.authorZhang, Y-
dc.contributor.authorZhang, B-
dc.contributor.authorFang, X-
dc.contributor.authorLiu, L-
dc.contributor.authorLuo, M-
dc.contributor.authorLiu, B-
dc.contributor.authorCHOW, LKY-
dc.contributor.authorChen, Q-
dc.contributor.authorHUANG, J-
dc.contributor.authorLee, VHF-
dc.contributor.authorLam, KO-
dc.contributor.authorLo, AWI-
dc.contributor.authorChen, Z-
dc.contributor.authorWang, Y-
dc.contributor.authorLee, AWM-
dc.contributor.authorGuan, XY-
dc.date.accessioned2021-06-18T14:54:09Z-
dc.date.available2021-06-18T14:54:09Z-
dc.date.issued2021-
dc.identifier.citationNature Communications, 2021, v. 12 n. 1, p. article no. 1540-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/300588-
dc.description.abstractThe tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME.-
dc.languageeng-
dc.publisherNature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html-
dc.relation.ispartofNature Communications-
dc.rightsNature Communications. Copyright © Nature Research: Fully open access journals.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleComprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma-
dc.typeArticle-
dc.identifier.emailKwong, DLW: dlwkwong@hku.hk-
dc.identifier.emailDai, W: weidai2@hku.hk-
dc.identifier.emailLiu, L: liuli71@hkucc.hku.hk-
dc.identifier.emailLee, VHF: vhflee@hku.hk-
dc.identifier.emailLam, KO: lamkaon@hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.emailLee, AWM: awmlee@hkucc.hku.hk-
dc.identifier.emailGuan, XY: xyguan@hku.hk-
dc.identifier.authorityKwong, DLW=rp00414-
dc.identifier.authorityDai, W=rp02146-
dc.identifier.authorityLiu, L=rp00268-
dc.identifier.authorityLee, VHF=rp00264-
dc.identifier.authorityLam, KO=rp01501-
dc.identifier.authorityChen, Z=rp00243-
dc.identifier.authorityLee, AWM=rp02056-
dc.identifier.authorityGuan, XY=rp00454-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-021-21795-z-
dc.identifier.pmid33750785-
dc.identifier.pmcidPMC7943808-
dc.identifier.scopuseid_2-s2.0-85102264764-
dc.identifier.hkuros322776-
dc.identifier.volume12-
dc.identifier.issue1-
dc.identifier.spagearticle no. 1540-
dc.identifier.epagearticle no. 1540-
dc.identifier.isiWOS:000627830600005-
dc.publisher.placeUnited Kingdom-

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