Prognostic Role Of MYBL2 In Patients With Osteosarcoma

PurposeOsteosarcoma is the most common malignant primary bone tumor in children and adolescents,and its high degree of invasiveness and metastasis is the leading cause of a patient’s poor prognosis.The genetic mechanism of osteosarcoma is complex,hindering the development of corresponding targeted therapy strategies and the emerging immunotherapy is also ineffective in osteosarcoma,and the treatment of osteosarcoma by traditional therapy has entered a bottleneck period.Therefore,it is imperative to find new markers for osteosarcoma typing therapy to improve the overall survival rate of osteosarcoma patients.Several studies at home and abroad have confirmed that MYBL2 plays an important role in cell cycle progression,cell survival and differentiation,and in a variety of tumors such as colorectal cancer;it shows that MYBL2 is associated with worse prognosis,which also provides new ideas for the early diagnosis of tumors,targeted therapy and prediction of tumor prognosis.However,the Expression of MYBL2 in osteosarcoma is unknown,and the predictive correlation has not been verified.The objectives of this study were to explore the expression level and clinical significance of MYBL2 in the tissues of osteosarcoma patients,to explore its possible mechanism of action in osteosarcoma,to judge the possibility of MYBL2 as a prognostic index for patients,and to provide a certain theoretical basis for finding new prognostic markers for osteosarcoma treatment.MethodsThe osteosarcoma single-cell dataset GSE152048 osteosarcoma sequencing and microarray datasets GSE87624,GSE42352 and GSE21257,were obtained from the GEO database.The osteosarcoma sequencing and methylation cohort TARGET was downloaded from the TARGET database,and the pan-cancer data was downloaded from the USCS Xena data portal.Imvigor210 immunotherapy cohort data were extracted from the R package IMvigor210 Core Biology version 1.0.0.The osteosarcoma immunohistochemistry cohort was derived from complete prechemotherapy osteosarcoma biopsy samples from our hospital followup.The single-cell dataset GSE152048 was subjected to quality control,filtering,normalization,normalization,linear dimensionality reduction,nonlinear dimensionality reduction,and cluster analysis using the Seurat package in R.Transcription factor activity in cell types was analyzed using the SCENIC algorithm,and cell-specific transcription factors were determined using an entropy-based algorithm.Predicted regulon-to-celltype correlations were validated using the SEEK database.This study used the R package survival for survival analysis,the R package clusterprofier for GO enrichment analysis,the KEGG enrichment analysis,and the R package gsva for ss GSEA analysis.The protein expression levels of MKI67 and MYBL2 in the Xiangya cohort were analyzed by immunohistochemistry.Assessment of immune cell infiltration in pancancer using the TIMER database.Correlation analysis was performed using the Spearman method,and the Wilcoxon rank-sum test was used to compare the differences between the two groups.Kaplan-Meier survival curves were used to present differences in survival analysis,and log-rank tests were used to examine differences between the two groups.P<0.05 was considered statistically significant.ResultsThe pattern of regulon activity in endothelial cells of different patients is similar,while the regulon activity is quite other in malignant osteoblasts with proliferative activity,indicating that the difference in regulon activity may cause the heterogeneity of osteosarcoma patients.MYLB2 is the most activated transcription factor in proliferating osteoblasts.MYBL2 is highly expressed in tumor tissues in osteosarcoma and pan-cancer.In osteosarcoma and pan-cancer,MYBL2 was associated with poor prognosis of patients,and the difference was statistically significant(P<0.05).The function of MYBL2 was studied,and gene enrichment analysis revealed that MYBL2 was positively correlated with cell proliferation and tumor immune pathways.Pan-cancer immune infiltration analysis showed that MYBL2 was associated with MDSC,Th2 cell infiltration,CD276,RELT gene expression,TMB,MSI.Finally,a nomogram for predicting the prognosis of osteosarcoma was established and validated based on MYBL2-related genes.ConclusionMYBL2 can be used as a potential marker to predict the prognosis of osteosarcoma.Osteosarcoma patients with high MYBL2 Expression may be more sensitive to methotrexate.MYBL2 may be a key factor in forming an inhibitory tumor immune microenvironment.Tumor patients with high MYBL2 Expression may be more suitable for immunotherapy.Osteosarcoma prognostic nomogram may provide new ideas for searching for predictive markers of osteosarcoma.