Molecular Classification Of Osteosarcoma And Characterization Of Tumor Characteristics Of Each Subtype

ObjectiveOsteosarcoma is a malignant interstitial tumor that tends to occur in adolescents.Surgery and neoadjuvant chemotherapy are the main treatment methods.The overall survival of patients has not changed in the past 30 years.There are large individual differences,and events such as drug resistance,recurrence and metastasis always occur in treatment.The prognosis is poor.At present,there is no effective molecular classification of osteosarcoma,and there has been no breakthrough in targeted therapy for the molecular characteristics of osteosarcoma.The purpose of this study is to reveal the characteristics of osteosarcoma differentiation from stem cells to tumor cells,define the three subtypes of osteosarcoma according to the molecular characteristics and differentiation of stem cell,and provide theoretical support for clinical drug development and clinical tumor diagnosis and treatment.MethodsIn this study,Single cell transcript data of 6 osteosarcoma cases and 9 cancellous bone cases were included in the joint analysis.After data cleansing,dimensionality reduction and clustering,After data cleaning,dimensionality reduction and clustering,each cell component was identified.From the perspectives of gene expression,transcription activation,pathway activation,and copy number variation,by comparing osteosarcoma cells and normal mesenchymal cells,we explored the unique transcription characteristics of tumor cells.By comparing tumor cell populations of different differentiation directions of osteosarcoma,we explored the molecular subtye of osteosarcoma,and revealed the interaction between tumor and microenvironment through the communication between each cell population.Finally,two cohorts of osteosarcoma were used to verify the feasibility of this molecular classification.ResultsWe identified 29 populations of cells,including tumor stem cell population,from osteosarcoma cells,showing the differentiation process of osteosarcoma.And from the differentiation direction of the stem cell population,three tumor populations with completely different gene expression,transcription activation,pathway activation and copy number variation are distinguished.44 characteristic genes were extracted from three tumor groups,and the prognosis was accurately classified in a public cohort and a clinical cohort.ConclusionThis study defined the stem cell population from osteosarcoma cells and clarified the difference between osteosarcoma stem cells and bone mesenchymal stem cells(BMSC).It also defines three molecular subtypes of osteosarcoma.The three subtypes of osteosarcoma have different transcriptional regulation models and the activation of different targeted therapy pathways.Finally,in two cohorts of osteosarcoma,it was proved that the molecular classification is an independent prognostic factor of osteosarcoma.