Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer Stemness
Genetic and epigenetic changes might facilitate the acquisition of stem cell-like phenotypes of tumors, resulting in worse patients outcome. Although the role of chromobox (CBX) domain proteins, a family of epigenetic factors that recognize specific histone marks, in the pathogenesis of several tumo...
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MDPI AG
2022-10-01
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Online Access: | https://www.mdpi.com/1422-0067/23/21/13083 |
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author | Patrycja Czerwinska Andrzej Adam Mackiewicz |
author_facet | Patrycja Czerwinska Andrzej Adam Mackiewicz |
author_sort | Patrycja Czerwinska |
collection | DOAJ |
description | Genetic and epigenetic changes might facilitate the acquisition of stem cell-like phenotypes of tumors, resulting in worse patients outcome. Although the role of chromobox (CBX) domain proteins, a family of epigenetic factors that recognize specific histone marks, in the pathogenesis of several tumor types is well documented, little is known about their association with cancer stemness. Here, we have characterized the relationship between the CBX family members’ expression and cancer stemness in liver, lung, pancreatic, and uterine tumors using publicly available TCGA and GEO databases and harnessing several bioinformatic tools (i.e., Oncomine, GEPIA2, TISIDB, GSCA, UALCAN, R2 platform, Enrichr, GSEA). We demonstrated that significant upregulation of CBX3 and downregulation of CBX7 are consistently associated with enriched cancer stem-cell-like phenotype across distinct tumor types. High CBX3 expression is observed in higher-grade tumors that exhibit stem cell-like traits, and CBX3-associated gene expression profiles are robustly enriched with stemness markers and targets for c-Myc transcription factor regardless of the tumor type. Similar to high-stemness tumors, CBX3-overexpressing cancers manifest a higher mutation load. On the other hand, higher-grade tumors are characterized by the significant downregulation of CBX7, and CBX7-associated gene expression profiles are significantly depleted with stem cell markers. In contrast to high-stemness tumors, cancer with CBX7 upregulation exhibit a lower mutation burden. Our results clearly demonstrate yet unrecognized association of high CBX3 and low CBX7 expression with cancer stem cell-like phenotype of solid tumors. |
first_indexed | 2024-03-09T19:00:42Z |
format | Article |
id | doaj.art-7d17eff66e4947b482204a3178c13a92 |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-09T19:00:42Z |
publishDate | 2022-10-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
spelling | doaj.art-7d17eff66e4947b482204a3178c13a922023-11-24T05:02:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211308310.3390/ijms232113083Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer StemnessPatrycja Czerwinska0Andrzej Adam Mackiewicz1Department of Cancer Immunology, Poznan University of Medical Sciences, 61-866 Poznan, PolandDepartment of Cancer Immunology, Poznan University of Medical Sciences, 61-866 Poznan, PolandGenetic and epigenetic changes might facilitate the acquisition of stem cell-like phenotypes of tumors, resulting in worse patients outcome. Although the role of chromobox (CBX) domain proteins, a family of epigenetic factors that recognize specific histone marks, in the pathogenesis of several tumor types is well documented, little is known about their association with cancer stemness. Here, we have characterized the relationship between the CBX family members’ expression and cancer stemness in liver, lung, pancreatic, and uterine tumors using publicly available TCGA and GEO databases and harnessing several bioinformatic tools (i.e., Oncomine, GEPIA2, TISIDB, GSCA, UALCAN, R2 platform, Enrichr, GSEA). We demonstrated that significant upregulation of CBX3 and downregulation of CBX7 are consistently associated with enriched cancer stem-cell-like phenotype across distinct tumor types. High CBX3 expression is observed in higher-grade tumors that exhibit stem cell-like traits, and CBX3-associated gene expression profiles are robustly enriched with stemness markers and targets for c-Myc transcription factor regardless of the tumor type. Similar to high-stemness tumors, CBX3-overexpressing cancers manifest a higher mutation load. On the other hand, higher-grade tumors are characterized by the significant downregulation of CBX7, and CBX7-associated gene expression profiles are significantly depleted with stem cell markers. In contrast to high-stemness tumors, cancer with CBX7 upregulation exhibit a lower mutation burden. Our results clearly demonstrate yet unrecognized association of high CBX3 and low CBX7 expression with cancer stem cell-like phenotype of solid tumors.https://www.mdpi.com/1422-0067/23/21/13083CBXHP1TRIM28Polycombcancer stemnessmRNA-SI |
spellingShingle | Patrycja Czerwinska Andrzej Adam Mackiewicz Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer Stemness International Journal of Molecular Sciences CBX HP1 TRIM28 Polycomb cancer stemness mRNA-SI |
title | Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer Stemness |
title_full | Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer Stemness |
title_fullStr | Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer Stemness |
title_full_unstemmed | Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer Stemness |
title_short | Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer Stemness |
title_sort | mining transcriptomic data to uncover the association between cbx family members and cancer stemness |
topic | CBX HP1 TRIM28 Polycomb cancer stemness mRNA-SI |
url | https://www.mdpi.com/1422-0067/23/21/13083 |
work_keys_str_mv | AT patrycjaczerwinska miningtranscriptomicdatatouncovertheassociationbetweencbxfamilymembersandcancerstemness AT andrzejadammackiewicz miningtranscriptomicdatatouncovertheassociationbetweencbxfamilymembersandcancerstemness |