Research On The Mechanism Of Abnormal Expression Of MIA3 In Ewing’s Sarcoma Prognosis

Ewing’s sarcoma is a small round cell sarcoma with similar morphology,originating from mesenchymal progenitor cells.Ewing’s sarcoma can occur in bone or soft tissue,and the most common primary site of disease in clinical practice is the long bone of the lower limb.The tumor is more common in children and adolescents,making it the second most common primary bone tumor in this population.Ewing’s sarcoma has a high degree of malignancy,with approximately 20-25% of patients already experiencing distant metastasis at the time of diagnosis.Ewing’s sarcoma is also prone to recurrence,and the 5-year survival rate of recurrent patients is less than 25%.After clinical research in multiple countries,the main treatment method for Ewing’s sarcoma is often a comprehensive treatment plan of surgery combined with radiotherapy and chemotherapy.This traditional comprehensive treatment method has greatly improved the survival time of patients with localized Ewing’s sarcoma.However,the pathological mechanism of Ewing’s sarcoma is complex,and the specific molecular mechanisms of its occurrence and development have not been fully revealed,making it impossible to implement precise and comprehensive diagnosis and treatment plans for Ewing’s sarcoma patients.With the development of genomics,more and more researchers are beginning to reveal the molecular mechanisms of Ewing’s sarcoma,in order to discover more effective biological therapy targets.At present,research has found that some biological therapy targets(such as IGF-1R or m TOR)are used to improve the prognosis of patients with Ewing’s sarcoma.Therefore,further research on efficient treatment targets,early diagnostic biomarkers,and mastering detailed pathogenesis have important practical significance and theoretical value.MIA3,also known as transport Golgi tissue protein 1(TANGO),is a member of the gene family of melanoma inhibitory activity.Previous studies have found that MIA3 is involved in the pathological processes of multiple diseases such as oral squamous cell carcinoma and colorectal cancer.However,there is currently no research on the relationship between MIA3 and the prognosis of Ewing’s sarcoma,so revealing the molecular mechanism of MIA3 in Ewing’s sarcoma has good research value.This study revealed the expression of MIA3 in Ewing’s sarcoma and explored the relationship between MIA3 and patient prognosis.And predict the molecular mechanisms that MIA3 may participate in the pathological process of Ewing’s sarcoma.Furthermore,a more comprehensive understanding of the pathogenesis of Ewing’s sarcoma can be provided,providing a potential target for the prognostic diagnosis and treatment of Ewing’s sarcoma.Research Method:1.Excluding samples with missing clinical information,the study obtained sequencing data from 56 cases of Ewing’s sarcoma in the ICGC public database.We also purchased human Ewing sarcoma cell lines(TC-32,RD-ES)and normal human bone marrow mesenchymal stem cells(HBMSC)from the cell bank for RT-qPCR to detect the expression abundance of MIA3 in Ewing sarcoma cell lines.2.Kaplan Meier survival analysis plots the patient’s survival curve,revealing whether the level of MIA3 expression is related to the patient’s survival time.And use the ROC curve to evaluate the credibility of MIA3 in the prognosis diagnosis of Juventus sarcoma.Subsequently,univariate and multivariate analyses were conducted to explore the intrinsic relationship between MIA3 expression levels and clinical relevant characteristics of patients,revealing independent risk factors for the prognosis of Ewing’s sarcoma.3.GSEA(Gene Set Enrichment Analysis)gene set enrichment analysis predicts the possible involvement of MIA3 in the biological and molecular mechanisms of pathological progression of Ewing’s sarcoma.4.Co expression analysis revealed multiple genes highly co correlated with MIA3 in Ewing’s sarcoma,and mapped corresponding co expression relationships.5.cMap drug prediction platform,obtain some small molecule drugs that can reduce the expression level of MIA3,and draw secondary and tertiary structural diagrams and chemical formulas of small molecule drugs.Result:1.The expression level of MIA3 in the experimental group of Ewing sarcoma cells(TC-32 and RD-ES)was higher than that in the control group of bone marrow mesenchymal stem cells.2.The Kaplan Meier survival analysis results showed that compared to the group of patients with low expression of MIA3,the 3-year and 5-year survival time of patients with high expression of MIA3 was significantly reduced.And the area under the three-year and five-year curves(AUC values)calculated by ROC were both greater than 0.7.The results of univariate analysis and multivariate regression analysis showed that high expression of MIA3 was a risk factor for Ewing’s sarcoma.3.The GSEA enrichment analysis results showed that the abnormally high expression of MIA3 was highly enriched in the MAPK signaling pathway,VEGF signaling pathway,and NOTCH signaling pathway.4.The results of gene co expression analysis showed that the five genes MCM3 AP,PDIA3P1,SYVN1,SETD1 A,and PDIA3 were most positively correlated with MIA3,while the five genes PIH1D2,RTCA-AS1,MED29,VPS9D1-AS1,and TCTEX1D2 were most negatively correlated with MIA3,with p-values less than0.001.5.The analysis results of the cMap platform suggest that small molecule compounds such as Atovaquone,reserpine,and Sanguinarine can inhibit the expression level of MIA3 in tumor cells.Research Conclusion:1.MIA3 is abnormally overexpressed in Ewing’s sarcoma,and patients with high expression of MIA3 have poor prognosis.2.High expression of MIA3 is an independent risk factor for poor prognosis in patients with Ewing’s sarcoma.3.The results of gene pool enrichment analysis indicate that MIA3 may be involved in the regulation of pathological progression of Ewing’s sarcoma through MAPK,VEGF,and NOTCH biological signaling pathways.4.Hematoporpine,reserpine,and atorvaquinone can inhibit the expression level of MIA3 in tumor cells,which has potential anti-tumor effects.