气候变化领域集成服务门户(CCPortal): Scaling concepts in 'omics: Nuclear lamin-B scales with tumor growth and often predicts poor prognosis, unlike fibrosis

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DOI	10.1073/pnas.2112940118
	Scaling concepts in 'omics: Nuclear lamin-B scales with tumor growth and often predicts poor prognosis, unlike fibrosis
	Vashisth M.; Cho S.; Irianto J.; Xia Y.; Wang M.; Hayes B.; Wieland D.; Wells R.; Jafarpour F.; Liu A.; Discher D.E.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:48
英文摘要	Physicochemical principles such as stoichiometry and fractal assembly can give rise to characteristic scaling between components that potentially include coexpressed transcripts. For key structural factors within the nucleus and extracellular matrix, we discover specific gene-gene scaling exponents across many of the 32 tumor types in The Cancer Genome Atlas, and we demonstrate utility in predicting patient survival as well as scaling-informed machine learning (SIML). All tumors with adjacent tissue data show cancerelevated proliferation genes, with some genes scaling with the nuclear filament LMNB1, including the transcription factor FOXM1 that we show directly regulates LMNB1. SIML shows that such regulated cancers cluster together with longer overall survival than dysregulated cancers, but high LMNB1 and FOXM1 in half of regulated cancers surprisingly predict poor survival, including for liver cancer. COL1A1 is also studied because it too increases in tumors, and a pan-cancer set of fibrosis genes shows substoichiometric scaling with COL1A1 but predicts patient outcome only for liver cancer- unexpectedly being prosurvival. Single-cell RNA-seq data show nontrivial scaling consistent with power laws from bulk RNA and protein analyses, and SIML segregates synthetic from contractile cancer fibroblasts. Our scaling approach thus yields fundamentals-based power laws relatable to survival, gene function, and experiments. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Expression; Fibrosis; Mechanobiology; Nucleus; Scaling
语种	英语
scopus关键词	collagen type 1; forkhead box protein M1; lamin B; collagen; DNA; lamin B; transcriptome; ACTA2 gene; Article; cancer cell; cancer classification; cancer prognosis; cancer survival; cancer tissue; carcinogenesis; cell cycle regulation; clinical article; cohort analysis; COL1A1 gene; controlled study; cytoskeleton; fibroblast; fibrosis; FOXM1 gene; gene cluster; gene control; gene function; human; human cell; human tissue; liver cancer; LMNB1 gene; machine learning; omics; oncogene; overall survival; prediction; protein analysis; RNA analysis; scale up; single cell RNA seq; stoichiometry; tumor growth; biology; cell nucleus; cell proliferation; cell survival; chemistry; extracellular matrix; fibrosis; gene expression profiling; gene expression regulation; genetics; genomics; Kaplan Meier method; liver tumor; mass spectrometry; mechanical stress; metabolism; neoplasm; procedures; prognosis; proteomics; treatment outcome; Cell Nucleus; Cell Proliferation; Cell Survival; Collagen; Computational Biology; DNA; Extracellular Matrix; Fibrosis; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genomics; Humans; Kaplan-Meier Estimate; Lamin Type B; Liver Neoplasms; Mass Spectrometry; Neoplasms; Oncogenes; Prognosis; Proteomics; Stress, Mechanical; Transcriptome; Treatment Outcome
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/250968
作者单位	Physical Science Oncology Center at Penn, University of Pennsylvania, Philadelphia, PA 19104, United States; Molecular and Cell Biophysics Laboratory, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Physics/Graduate Group in Physics, University of Pennsylvania, Philadelphia, PA 19104, United States
推荐引用方式 GB/T 7714	Vashisth M.,Cho S.,Irianto J.,et al. Scaling concepts in 'omics: Nuclear lamin-B scales with tumor growth and often predicts poor prognosis, unlike fibrosis[J],2021,118(48).
APA	Vashisth M..,Cho S..,Irianto J..,Xia Y..,Wang M..,...&Discher D.E..(2021).Scaling concepts in 'omics: Nuclear lamin-B scales with tumor growth and often predicts poor prognosis, unlike fibrosis.Proceedings of the National Academy of Sciences of the United States of America,118(48).
MLA	Vashisth M.,et al."Scaling concepts in 'omics: Nuclear lamin-B scales with tumor growth and often predicts poor prognosis, unlike fibrosis".Proceedings of the National Academy of Sciences of the United States of America 118.48(2021).