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Gibbs process distinguishes survival and reveals contact-inhibition genes in Glioblastoma multiforme
Tumor growth is a spatiotemporal birth-and-death process with loss of heterotypic contact-inhibition of locomotion (CIL) of tumor cells promoting invasion and metastasis. Therefore, representing tumor cells as two-dimensional points, we can expect the tumor tissues in histology slides to reflect rea...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934342/ https://www.ncbi.nlm.nih.gov/pubmed/36795646 http://dx.doi.org/10.1371/journal.pone.0277176 |
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author | Jahedi, Afrooz Kumar, Gayatri Kannan, Lavanya Agarwal, Tarjani Huse, Jason Bhat, Krishna Kannan, Kasthuri |
author_facet | Jahedi, Afrooz Kumar, Gayatri Kannan, Lavanya Agarwal, Tarjani Huse, Jason Bhat, Krishna Kannan, Kasthuri |
author_sort | Jahedi, Afrooz |
collection | PubMed |
description | Tumor growth is a spatiotemporal birth-and-death process with loss of heterotypic contact-inhibition of locomotion (CIL) of tumor cells promoting invasion and metastasis. Therefore, representing tumor cells as two-dimensional points, we can expect the tumor tissues in histology slides to reflect realizations of spatial birth-and-death process which can be mathematically modeled to reveal molecular mechanisms of CIL, provided the mathematics models the inhibitory interactions. Gibbs process as an inhibitory point process is a natural choice since it is an equilibrium process of the spatial birth-and-death process. That is if the tumor cells maintain homotypic contact inhibition, the spatial distributions of tumor cells will result in Gibbs hard core process over long time scales. In order to verify if this is the case, we applied the Gibbs process to 411 TCGA Glioblastoma multiforme patient images. Our imaging dataset included all cases for which diagnostic slide images were available. The model revealed two groups of patients, one of which - the “Gibbs group,” showed the convergence of the Gibbs process with significant survival difference. Further smoothing the discretized (and noisy) inhibition metric, for both increasing and randomized survival time, we found a significant association of the patients in the Gibbs group with increasing survival time. The mean inhibition metric also revealed the point at which the homotypic CIL establishes in tumor cells. Besides, RNAseq analysis between patients with loss of heterotypic CIL and intact homotypic CIL in the Gibbs group unveiled cell movement gene signatures and differences in Actin cytoskeleton and RhoA signaling pathways as key molecular alterations. These genes and pathways have established roles in CIL. Taken together, our integrated analysis of patient images and RNAseq data provides for the first time a mathematical basis for CIL in tumors, explains survival as well as uncovers the underlying molecular landscape for this key tumor invasion and metastatic phenomenon. |
format | Online Article Text |
id | pubmed-9934342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-99343422023-02-17 Gibbs process distinguishes survival and reveals contact-inhibition genes in Glioblastoma multiforme Jahedi, Afrooz Kumar, Gayatri Kannan, Lavanya Agarwal, Tarjani Huse, Jason Bhat, Krishna Kannan, Kasthuri PLoS One Research Article Tumor growth is a spatiotemporal birth-and-death process with loss of heterotypic contact-inhibition of locomotion (CIL) of tumor cells promoting invasion and metastasis. Therefore, representing tumor cells as two-dimensional points, we can expect the tumor tissues in histology slides to reflect realizations of spatial birth-and-death process which can be mathematically modeled to reveal molecular mechanisms of CIL, provided the mathematics models the inhibitory interactions. Gibbs process as an inhibitory point process is a natural choice since it is an equilibrium process of the spatial birth-and-death process. That is if the tumor cells maintain homotypic contact inhibition, the spatial distributions of tumor cells will result in Gibbs hard core process over long time scales. In order to verify if this is the case, we applied the Gibbs process to 411 TCGA Glioblastoma multiforme patient images. Our imaging dataset included all cases for which diagnostic slide images were available. The model revealed two groups of patients, one of which - the “Gibbs group,” showed the convergence of the Gibbs process with significant survival difference. Further smoothing the discretized (and noisy) inhibition metric, for both increasing and randomized survival time, we found a significant association of the patients in the Gibbs group with increasing survival time. The mean inhibition metric also revealed the point at which the homotypic CIL establishes in tumor cells. Besides, RNAseq analysis between patients with loss of heterotypic CIL and intact homotypic CIL in the Gibbs group unveiled cell movement gene signatures and differences in Actin cytoskeleton and RhoA signaling pathways as key molecular alterations. These genes and pathways have established roles in CIL. Taken together, our integrated analysis of patient images and RNAseq data provides for the first time a mathematical basis for CIL in tumors, explains survival as well as uncovers the underlying molecular landscape for this key tumor invasion and metastatic phenomenon. Public Library of Science 2023-02-16 /pmc/articles/PMC9934342/ /pubmed/36795646 http://dx.doi.org/10.1371/journal.pone.0277176 Text en © 2023 Jahedi et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Jahedi, Afrooz Kumar, Gayatri Kannan, Lavanya Agarwal, Tarjani Huse, Jason Bhat, Krishna Kannan, Kasthuri Gibbs process distinguishes survival and reveals contact-inhibition genes in Glioblastoma multiforme |
title | Gibbs process distinguishes survival and reveals contact-inhibition genes in Glioblastoma multiforme |
title_full | Gibbs process distinguishes survival and reveals contact-inhibition genes in Glioblastoma multiforme |
title_fullStr | Gibbs process distinguishes survival and reveals contact-inhibition genes in Glioblastoma multiforme |
title_full_unstemmed | Gibbs process distinguishes survival and reveals contact-inhibition genes in Glioblastoma multiforme |
title_short | Gibbs process distinguishes survival and reveals contact-inhibition genes in Glioblastoma multiforme |
title_sort | gibbs process distinguishes survival and reveals contact-inhibition genes in glioblastoma multiforme |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934342/ https://www.ncbi.nlm.nih.gov/pubmed/36795646 http://dx.doi.org/10.1371/journal.pone.0277176 |
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