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Re-wiring and gene expression changes of AC025034.1 and ATP2B1 play complex roles in early-to-late breast cancer progression
BACKGROUND: Elucidating the dynamic topological changes across different stages of breast cancer, called stage re-wiring, could lead to identifying key latent regulatory signatures involved in cancer progression. Such dynamic regulators and their functions are mostly unknown. Here, we reconstructed...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759272/ https://www.ncbi.nlm.nih.gov/pubmed/35031021 http://dx.doi.org/10.1186/s12863-021-01015-9 |
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author | Khoshbakht, Samane Mokhtari, Majid Moravveji, Sayyed Sajjad Azimzadeh Jamalkandi, Sadegh Masoudi-Nejad, Ali |
author_facet | Khoshbakht, Samane Mokhtari, Majid Moravveji, Sayyed Sajjad Azimzadeh Jamalkandi, Sadegh Masoudi-Nejad, Ali |
author_sort | Khoshbakht, Samane |
collection | PubMed |
description | BACKGROUND: Elucidating the dynamic topological changes across different stages of breast cancer, called stage re-wiring, could lead to identifying key latent regulatory signatures involved in cancer progression. Such dynamic regulators and their functions are mostly unknown. Here, we reconstructed differential co-expression networks for four stages of breast cancer to assess the dynamic patterns of cancer progression. A new computational approach was applied to identify stage-specific subnetworks for each stage. Next, prognostic traits of genes and the efficiency of stage-related groups were evaluated and validated, using the Log-Rank test, SVM classifier, and sample clustering. Furthermore, by conducting the stepwise VIF-feature selection method, a Cox-PH model was developed to predict patients’ risk. Finally, the re-wiring network for prognostic signatures was reconstructed and assessed across stages to detect gain/loss, positive/negative interactions as well as rewired-hub nodes contributing to dynamic cancer progression. RESULTS: After having implemented our new approach, we could identify four stage-specific core biological pathways. We could also detect an essential non-coding RNA, AC025034.1, which is not the only antisense to ATP2B1 (cell proliferation regulator), but also revealed a statistically significant stage-descending pattern; Moreover, AC025034.1 revealed both a dynamic topological pattern across stages and prognostic trait. We also identified a high-performance Overall-Survival-Risk model, including 12 re-wired genes to predict patients’ risk (c-index = 0.89). Finally, breast cancer-specific prognostic biomarkers of LINC01612, AC092142.1, and AC008969.1 were identified. CONCLUSIONS: In summary new scoring method highlighted stage-specific core pathways for early-to-late progressions. Moreover, detecting the significant re-wired hub nodes indicated stage-associated traits, which reflects the importance of such regulators from different perspectives. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12863-021-01015-9. |
format | Online Article Text |
id | pubmed-8759272 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-87592722022-01-18 Re-wiring and gene expression changes of AC025034.1 and ATP2B1 play complex roles in early-to-late breast cancer progression Khoshbakht, Samane Mokhtari, Majid Moravveji, Sayyed Sajjad Azimzadeh Jamalkandi, Sadegh Masoudi-Nejad, Ali BMC Genom Data Research BACKGROUND: Elucidating the dynamic topological changes across different stages of breast cancer, called stage re-wiring, could lead to identifying key latent regulatory signatures involved in cancer progression. Such dynamic regulators and their functions are mostly unknown. Here, we reconstructed differential co-expression networks for four stages of breast cancer to assess the dynamic patterns of cancer progression. A new computational approach was applied to identify stage-specific subnetworks for each stage. Next, prognostic traits of genes and the efficiency of stage-related groups were evaluated and validated, using the Log-Rank test, SVM classifier, and sample clustering. Furthermore, by conducting the stepwise VIF-feature selection method, a Cox-PH model was developed to predict patients’ risk. Finally, the re-wiring network for prognostic signatures was reconstructed and assessed across stages to detect gain/loss, positive/negative interactions as well as rewired-hub nodes contributing to dynamic cancer progression. RESULTS: After having implemented our new approach, we could identify four stage-specific core biological pathways. We could also detect an essential non-coding RNA, AC025034.1, which is not the only antisense to ATP2B1 (cell proliferation regulator), but also revealed a statistically significant stage-descending pattern; Moreover, AC025034.1 revealed both a dynamic topological pattern across stages and prognostic trait. We also identified a high-performance Overall-Survival-Risk model, including 12 re-wired genes to predict patients’ risk (c-index = 0.89). Finally, breast cancer-specific prognostic biomarkers of LINC01612, AC092142.1, and AC008969.1 were identified. CONCLUSIONS: In summary new scoring method highlighted stage-specific core pathways for early-to-late progressions. Moreover, detecting the significant re-wired hub nodes indicated stage-associated traits, which reflects the importance of such regulators from different perspectives. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12863-021-01015-9. BioMed Central 2022-01-14 /pmc/articles/PMC8759272/ /pubmed/35031021 http://dx.doi.org/10.1186/s12863-021-01015-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Khoshbakht, Samane Mokhtari, Majid Moravveji, Sayyed Sajjad Azimzadeh Jamalkandi, Sadegh Masoudi-Nejad, Ali Re-wiring and gene expression changes of AC025034.1 and ATP2B1 play complex roles in early-to-late breast cancer progression |
title | Re-wiring and gene expression changes of AC025034.1 and ATP2B1 play complex roles in early-to-late breast cancer progression |
title_full | Re-wiring and gene expression changes of AC025034.1 and ATP2B1 play complex roles in early-to-late breast cancer progression |
title_fullStr | Re-wiring and gene expression changes of AC025034.1 and ATP2B1 play complex roles in early-to-late breast cancer progression |
title_full_unstemmed | Re-wiring and gene expression changes of AC025034.1 and ATP2B1 play complex roles in early-to-late breast cancer progression |
title_short | Re-wiring and gene expression changes of AC025034.1 and ATP2B1 play complex roles in early-to-late breast cancer progression |
title_sort | re-wiring and gene expression changes of ac025034.1 and atp2b1 play complex roles in early-to-late breast cancer progression |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759272/ https://www.ncbi.nlm.nih.gov/pubmed/35031021 http://dx.doi.org/10.1186/s12863-021-01015-9 |
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