Brain metastases: It takes two factors for a primary cancer to metastasize to brain
Brain metastasis of a cancer is a malignant disease with high mortality, but the cause and the molecular mechanism remain largely unknown. Using the samples of primary tumors of 22 cancer types in the TCGA database, we have performed a computational study of their transcriptomic data to investigate...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1003715/full |
| _version_ | 1828388420553015296 |
|---|---|
| author | Dingyun Liu Dingyun Liu Jun Bai Jun Bai Qian Chen Qian Chen Renbo Tan Renbo Tan Zheng An Zheng An Jun Xiao Jun Xiao Yingwei Qu Yingwei Qu Ying Xu Ying Xu |
| author_facet | Dingyun Liu Dingyun Liu Jun Bai Jun Bai Qian Chen Qian Chen Renbo Tan Renbo Tan Zheng An Zheng An Jun Xiao Jun Xiao Yingwei Qu Yingwei Qu Ying Xu Ying Xu |
| author_sort | Dingyun Liu |
| collection | DOAJ |
| description | Brain metastasis of a cancer is a malignant disease with high mortality, but the cause and the molecular mechanism remain largely unknown. Using the samples of primary tumors of 22 cancer types in the TCGA database, we have performed a computational study of their transcriptomic data to investigate the drivers of brain metastases at the basic physics and chemistry level. Our main discoveries are: (i) the physical characteristics, namely electric charge, molecular weight, and the hydrophobicity of the extracellular structures of the expressed transmembrane proteins largely affect a primary cancer cell’s ability to cross the blood-brain barrier; and (ii) brain metastasis may require specific functions provided by the activated enzymes in the metastasizing primary cancer cells for survival in the brain micro-environment. Both predictions are supported by published experimental studies. Based on these findings, we have built a classifier to predict if a given primary cancer may have brain metastasis, achieving the accuracy level at AUC = 0.92 on large test sets. |
| first_indexed | 2024-12-10T06:12:59Z |
| format | Article |
| id | doaj.art-e3182d9c2b2647ad960d61aa546bc9da |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T06:12:59Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e3182d9c2b2647ad960d61aa546bc9da2022-12-22T01:59:31ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-09-011210.3389/fonc.2022.10037151003715Brain metastases: It takes two factors for a primary cancer to metastasize to brainDingyun Liu0Dingyun Liu1Jun Bai2Jun Bai3Qian Chen4Qian Chen5Renbo Tan6Renbo Tan7Zheng An8Zheng An9Jun Xiao10Jun Xiao11Yingwei Qu12Yingwei Qu13Ying Xu14Ying Xu15Center for Cancer Systems Biology, China-Japan Union Hospital of Jilin University, Changchun, ChinaCollege of Computer Science and Technology, Jilin University, Changchun, ChinaCenter for Cancer Systems Biology, China-Japan Union Hospital of Jilin University, Changchun, ChinaSchool of Artificial Intelligence, Jilin University, Changchun, ChinaCenter for Cancer Systems Biology, China-Japan Union Hospital of Jilin University, Changchun, ChinaCollege of Computer Science and Technology, Jilin University, Changchun, ChinaCenter for Cancer Systems Biology, China-Japan Union Hospital of Jilin University, Changchun, ChinaCollege of Computer Science and Technology, Jilin University, Changchun, ChinaCenter for Cancer Systems Biology, China-Japan Union Hospital of Jilin University, Changchun, ChinaComputational Systems Biology Lab, Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, The University of Georgia, Athens, GA, United StatesCenter for Cancer Systems Biology, China-Japan Union Hospital of Jilin University, Changchun, ChinaCollege of Computer Science and Technology, Jilin University, Changchun, ChinaCenter for Cancer Systems Biology, China-Japan Union Hospital of Jilin University, Changchun, ChinaCollege of Computer Science and Technology, Jilin University, Changchun, ChinaCenter for Cancer Systems Biology, China-Japan Union Hospital of Jilin University, Changchun, ChinaComputational Systems Biology Lab, Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, The University of Georgia, Athens, GA, United StatesBrain metastasis of a cancer is a malignant disease with high mortality, but the cause and the molecular mechanism remain largely unknown. Using the samples of primary tumors of 22 cancer types in the TCGA database, we have performed a computational study of their transcriptomic data to investigate the drivers of brain metastases at the basic physics and chemistry level. Our main discoveries are: (i) the physical characteristics, namely electric charge, molecular weight, and the hydrophobicity of the extracellular structures of the expressed transmembrane proteins largely affect a primary cancer cell’s ability to cross the blood-brain barrier; and (ii) brain metastasis may require specific functions provided by the activated enzymes in the metastasizing primary cancer cells for survival in the brain micro-environment. Both predictions are supported by published experimental studies. Based on these findings, we have built a classifier to predict if a given primary cancer may have brain metastasis, achieving the accuracy level at AUC = 0.92 on large test sets.https://www.frontiersin.org/articles/10.3389/fonc.2022.1003715/fullbrain metastasismetabolic reprogrammingbrain microenvironmentseed-soil hypothesisblood-brain barrier |
| spellingShingle | Dingyun Liu Dingyun Liu Jun Bai Jun Bai Qian Chen Qian Chen Renbo Tan Renbo Tan Zheng An Zheng An Jun Xiao Jun Xiao Yingwei Qu Yingwei Qu Ying Xu Ying Xu Brain metastases: It takes two factors for a primary cancer to metastasize to brain Frontiers in Oncology brain metastasis metabolic reprogramming brain microenvironment seed-soil hypothesis blood-brain barrier |
| title | Brain metastases: It takes two factors for a primary cancer to metastasize to brain |
| title_full | Brain metastases: It takes two factors for a primary cancer to metastasize to brain |
| title_fullStr | Brain metastases: It takes two factors for a primary cancer to metastasize to brain |
| title_full_unstemmed | Brain metastases: It takes two factors for a primary cancer to metastasize to brain |
| title_short | Brain metastases: It takes two factors for a primary cancer to metastasize to brain |
| title_sort | brain metastases it takes two factors for a primary cancer to metastasize to brain |
| topic | brain metastasis metabolic reprogramming brain microenvironment seed-soil hypothesis blood-brain barrier |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1003715/full |
| work_keys_str_mv | AT dingyunliu brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT dingyunliu brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT junbai brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT junbai brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT qianchen brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT qianchen brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT renbotan brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT renbotan brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT zhengan brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT zhengan brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT junxiao brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT junxiao brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT yingweiqu brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT yingweiqu brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT yingxu brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain AT yingxu brainmetastasesittakestwofactorsforaprimarycancertometastasizetobrain |