| Objective: Prosthesis-related complications,after the reconstruction with endoprosthesis following resection of tumors around the knee,remain an unresolved problem which necessitate multiple operations,including debridement,tumor resection,revision of the prosthesis,and even an amputation.In addition,the management of metastatic sarcoma of knee is challenging,and the prognosis of the patients is even poor.Primarily,the purpose of the current study was to investigate the following questions:(1)the overall survival time of the patients;(2)the overall survival time of the prosthesis after reconstruction;(3)the related complications of prosthetic limb salvage surgery in patients encountered knee reconstruction with endoprostheses for bone and soft tissue tumors around the knee joint;(4)identify the risk factors affecting the prosthesis survival.Secondly,in order to further explore the metastatic mechanism of the sarcoma around the knee,an experiment was carried out,to screen new therapeutic targets related to molecular prognosis,so as to provide reference for the development of new anti-tumor drugs and the prevention,diagnosis,treatment and prognosis of clinical osteosarcoma.Methods: A retrospectively review was carried out to select our two centers maintained database for patients who underwent reconstruction of the distal femur and/or proximal tibia due to bone or soft tissue tumors in our center between April1995 and August 2018.A total of 203 patients were included,including 123 males(123/203,60.6%)and 80(80/203,39.4%)females,ranging in age from 14 to 77 years(mean: 33.5±17.3 years,median:27.0 years).Randomly the cohort was divided into training(n= 156)samples and validation(n= 47)samples.Univariable COX analysis was used for initially identifying potential independent predictors of prosthesis survival with the training group(p< 0.150).Multivariate COX proportional hazard model was selected to identify final significant prognostic factors influential of the prosthesis.Using these significant predictors,a graphic nomogram,and an online dynamic nomogram were created for predicting the prosthetic survival.C-index and calibration curve were used for evaluate the discrimination ability and accuracy of the novel model,both in the training and validation groups.To explore the mechanism of metastasis of the osteosarcoma,the expression of miRNA-20b-5p in osteosarcoma tissues and cells were confirmed by RT-PCR,the expression of miRNA-20b-5p was interfered by transfection of miRNA-20b-5p mimics and inhibitors.CCK-8 assay was used to detect the effect of miRNA-20b-5p on cell proliferation,the migration effect of miRNA-20b-5p on osteosarcoma cells was detected by Transwell,the effects of miRNA-20b-5p on cell metabolism were detected by glucose consumption and lactate production.RT-PCR and Western blot were used to detect the regulation of HIF-1α expression by miRNA-20b-5p,and the molecular mechanism was explored by dual luciferase reporter assay.Results: The 1-,5-,and 10-year survival rates were 96.4%,85.1,and 74.8%,respectively for all patients.The survival rates of all prosthesis for all patients at 1,5and 10 years were 95.6%,87.5% and 81.2%,respectively.The prosthesis survival at 1-,5-,and 10-year were 94.0,90.8,and 83.0%,and 96.7,85.8,67.5 and 76.9% in training and validation groups,respectively.Anatomic sites,length of resection and length of prosthetic stem were independently associated with the prosthetic failure according to multivariate COX regression model(p<0.05).⑶ Using these three significant predictors,a graphical nomogram and an online dynamic nomogram model were generated.The C-indexes in training and validation groups were 0.717 and 0.726 respectively,demonstrating favourable discrimination ability of the novel model.And the calibration curve at each time point showed favorable consistency between the predicted and actual survival rates in training and validation samples.Following the primary implantation of the prosthesis,prosthesis related complications occured in 85(85 / 203,41.80%)patients and 183 operations were performed.The expression of miRNA-20b-5p was decreased in osteosarcoma tissues and cell lines.Over-expression of miRNA-20b-5p in osteosarcoma cells,HIF-1α was inhibited due to the binding of miRNA-20b-5p to the 3 ’-UTR of HIF-1α,which can inhibit the proliferation,migration and metabolism of osteosarcoma cells.However,interfering with the expression of miRNA-20b-5p can increase the expression of HIF-1α and promote the proliferation,migration and metabolism of osteosarcoma cells.Conclusions: Prosthetic limb salvage surgery was an effective method for the treatment of tumors around the knee.The length of resection,anatomical location of tumor,and length of prosthetic stem were significantly associated with prosthetic survival in patients operated for tumor around knee.A user-friendly novel online model model,with favorable discrimination ability and accuracy,was generated to help surgeons predict the survival of the prosthesis.However,the proximal tibial and distal femoral endoprostheses were particularly at risk for medium and long-term endoprosthetic complications which required additional surgical procedures indicates that tumor endoprostheses need to be further studied,and improvements in surgical technique and component design.The expression of HIF-1a was significantly increased,while miRNA-20b-5p obviously decreased in OS patients and OS cell lines compared with healthy controls.Highly expressed miRNA-20b-5p by means of genetic tools inhibited the expression of HIF-1 α,which subsequently inhibited the behavior of the molecule of the sarcomas,including the growth,themigration and the metabolism.Mi RNA-20b-5p and HIF-1α may have a closely relationship with the metastasis of osteosarcoma.These results may provide a potential therapeutic strategy for osteosarcoma. |
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