Screening Of Bone-derived Secreted Factors And Analysis Of Their Role In Bone Metastasis Of Breast Cancer

The skeletal system is one of the most important organs of the body.In addition to providing the most basic support for the human body,its important role as an endocrine organ has also been elucidated.Studies have shown that the secreted factors of cells in the bone may be responsible for the maintenance of bone homeostasis,The basis and key factors for maintaining the homeostasis of various organ systems in the body.However,few bone-derived factors have been found so far,so that the role of bone endocrine function in systemic homeostasis regulation and disease occurrence is far underestimated.Therefore,this paper aims to screen a large number of bone-derived factors as comprehensively as possible and describe their basic features and explore their applications.In this paper,21 kinds of tissues of 3-month-old C57BL/6 strain mice(3-7 cases each,including 5 kinds of bone tissues in different parts-long bone metaphysis,long bone midsection,cranium,spinal bone and costal cartilage and 16 kinds of Soft tissue-heart,liver,spleen,lung,kidney,brain,large intestine,small intestine,skin,muscle,bone marrow,female reproductive tissue,male reproductive tissue,inguinal fat,paragonadal fat,and brown fat),80 samples for transcriptome high Through-through sequencing,bone-specific high-expression genes were screened out through differential analysis,and bone-specific high-expression genes encoding secreted proteins were screened out in combination with GO-CC term annotation,uniprot annotation,signal peptide and transmembrane regions of their gene-encoded proteins,Constitute the final bone-derived factor collection.Then explore the function of the bone-derived factor set.In addition to annotating some classic pathways related to the development of the skeletal muscle system and the maintenance of bone homeostasis,some pathways related to the regulation of extraskeletal organs and systems are also annotated.To determine the secretory origin of these osteogenic factors,we integrated multiple single-cell data,using random perturbations and the expression of osteogenic factors in cell populations to determine the localization of osteogenic factors,some known classical osteogenic factors demonstrated The reliability of our bone-derived factor localization prediction;then use CellPhoneDB,CellChat tools to predict intercellular communication,and explore its important role in regulating extraskeletal organs and systems.Breast cancer is one of the cancers most prone to bone metastasis.This article aims to explore the role of bone-derived factors in this process and provide ideas for the diagnosis and treatment of bone metastasis.This topic also downloaded breast cancer(BRCA)from the TCGA database Based on the transcriptome expression data and the clinical data corresponding to the sample,a weighted co-expression network(WGCNA)was constructed based on the differential genes of bone metastasis,and then the key modules significantly correlated with the sample bone-derived factor set and the cancer Hallmark enrichment score were screened,and the modules with Key genes that are significantly related to bone-derived factors,and finally download 318 TF sets that play an important role in the development of cancer from the Cistrome database,combined with TF,bone-derived factors and bone-derived factor-related hubgenes,and Hallmarks that are significantly related to key modules,Constructed the bone-derived factor-related specific regulatory network of breast cancer bone metastasis,providing direction for the mechanism of breast cancer bone metastasis,its diagnosis and related treatment.In summary,this paper screened secreted bone tissue-specific high-expression genes on a large scale through high-throughput sequencing,which constituted the bonederived factor collection in this paper,and then made functional annotations,cell localization and other basic information of bone-derived factors.Described and further explored the use of bone-derived factors in the regulation of extraskeletal organs and systems and bone metastasis of breast cancer.