In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 5 ( 2022-5-19), p. e0268626-
Abstract:
Significant alterations in signaling pathways and transcriptional regulatory programs together represent major hallmarks of many cancers. These, among all, include the reactivation of stemness, which is registered by the expression of pathways that are active in the embryonic stem cells (ESCs). Here, we assembled gene sets that reflect the stemness and proliferation signatures and used them to analyze a large panel of RNA-seq data from The Cancer Genome Atlas (TCGA) Consortium in order to specifically assess the expression of stemness-related and proliferation-related genes across a collection of different tumor types. We introduced a metric that captures the collective similarity of the expression profile of a tumor to that of ESCs, which showed that stemness and proliferation signatures vary greatly between different tumor types. We also observed a high degree of intertumoral heterogeneity in the expression of stemness- and proliferation-related genes, which was associated with increased hazard ratios in a fraction of tumors and mirrored by high intratumoral heterogeneity and a remarkable stemness capacity in metastatic lesions across cancer cells in single cell RNA-seq datasets. Taken together, these results indicate that the expression of stemness signatures is highly heterogeneous and cannot be used as a universal determinant of cancer. This calls into question the universal validity of diagnostic tests that are based on stem cell markers.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0268626
DOI:
10.1371/journal.pone.0268626.g001
DOI:
10.1371/journal.pone.0268626.g002
DOI:
10.1371/journal.pone.0268626.g003
DOI:
10.1371/journal.pone.0268626.g004
DOI:
10.1371/journal.pone.0268626.g005
DOI:
10.1371/journal.pone.0268626.g006
DOI:
10.1371/journal.pone.0268626.g007
DOI:
10.1371/journal.pone.0268626.g008
DOI:
10.1371/journal.pone.0268626.s001
DOI:
10.1371/journal.pone.0268626.s002
DOI:
10.1371/journal.pone.0268626.s003
DOI:
10.1371/journal.pone.0268626.s004
DOI:
10.1371/journal.pone.0268626.s005
DOI:
10.1371/journal.pone.0268626.s006
DOI:
10.1371/journal.pone.0268626.s007
DOI:
10.1371/journal.pone.0268626.s008
DOI:
10.1371/journal.pone.0268626.s009
DOI:
10.1371/journal.pone.0268626.s010
DOI:
10.1371/journal.pone.0268626.s011
DOI:
10.1371/journal.pone.0268626.s012
DOI:
10.1371/journal.pone.0268626.s013
DOI:
10.1371/journal.pone.0268626.s014
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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