Correlation Analysis Of The Direct Bilirubin Level Before Treat Ment And Prognosis Of Patients With Osteosarcoma And The Establishment Of A Nomogram

Background and ObjectiveOsteosarcoma is a malignant tumor that originates from mesenchymal tissues and is the most common primary malignant tumor of bones.Osteosarcoma account for less than 0.2%of all cancers.Although the incidence of osteosarcoma is low,the prognosis is poor.There is often no typical clinical manifestations in the early stage,and it is easily metastasized to the lungs through the bloodstream,which is the main cause of death in patients with osteosarcoma.In the past,the main treatment for osteosarcoma was surgery.After continuous exploration,the current standard treatments are neoadjuvant chemotherapy,surgery,and postoperative chemotherapy.Although the survival rate of patients is improved,it is easy to relapse locally and distantly after drug resistance.Metastasis or even death,the overall survival rate is still low.Therefore,effective prognostic biomarkers are extremely important for the prevention and treatment of osteosarcoma.Among the serum markers,alkaline phosphatase and lactate dehydrogenase are the most extensively studied,and they are related to the prognosis of many tumors including osteosarcoma,but this is far from enough.More serum markers are needed to guide individual diagnosis and treatment of osteosarcoma patients.The predictive role of bilirubin in many tumors has been confirmed,elevated bilirubin is associated with a good prognosis in lung cancer,colorectal cancer,liver cancer,but there is no research on bilirubin in osteosarcoma.Therefore,this study chose direct bilirubin as the target to study its predictive role in the prognosis of osteosarcoma.ObjectiveTo investigate the relationship between pretreatment peripheral blood direct bilirubin(DBIL)and clinical characteristics and prognosis of patients with osteosarcoma and to establish an effective prognostic nomogram.Dates and MethodsTo retrospectively collect detailed clinicopathological data and blood sample parameters including total bilirubin(TBIL)、direct bilirubin(DBIL)、alkaline phosphatase(ALP)、lactate dehydrogenase(LDH)of 120 patients who were admitted to the First Affiliated Hospital of Zhengzhou University from June 2012 to December 2019 and were confirmed to be osteosarcoma by histopathology.Chi-square test was used to analyze the correlation between DBIL and clinical characteristics of osteosarcoma patients,spearman correlation analysis was used to analyze the linear correlation between DBIL and TBIL,univariate and multivariate COX regression was used to analyze the independent prognostic factors of osteosarcoma patients,and effective prognostic nomograms were conducted based on independent prognostic factor,consistency index(C-index)and calibration curve defined the prediction accuracy and discriminative power of the nomogram.Results1.The median overall survival(OS)of 120 patients with osteosarcoma was 45 months,and the 1-year,3-year,5-year survival rates were respectively 95%,67%,40%.2.The DBIL exhibited a significant positive relationship with total bilirubin(TBIL)(r=0.854,P<0.001)and was an independent prognostic factor for the progression-free survival(PFS)(HR:0.558,95%CI:0.344-0.908,P=0.019).In addition,DBIL<3.5umol/L predicted a poor OS and PFS in patients with osteosarcoma(P<0.05)and TBIL<5.8umol/L predicted a poor OS(P<0.05).According to the relationship between DBIL and TBIL,120 patients with osteosarcoma were divided into two groups:low-risk group(TBIL≥5.8umon/L and DBIL≥3.5umol/L)and high-risk group(TBILL<5.8umol/L or DBIL<3.5umol/L),the high-risk group had a shorter OS than the low-risk group in patients with osteosarcoma(P<0.05).3.No neoadjuvant chemotherapy and ALP≥123U/L are independent risk factors for PFS.Distant metastasis is an independent prognostic factor of OS.LDH≥213U/L is an independent influence factor of PFS and OS.4.Effective prognostic nomograms were conducted based on independent prognostic factor,including DBIL,LDH,ALP,Neoadjuvant chemotherapy(NAC),Distant metastasis.The C-index used to predict PFS and OS were respectively 0.657,95%CI(0.512-0.799);0.712,95%CI(0.504-0.920),higher than cTNM:0.558,95%CI(0.454-0.662);0.616,95%CI(0.438-0.794).The nomogram can predict the survival of patients with osteosarcoma(P<0.05)better.ConclusionThe level of peripheral blood DBIL before treatment independently affects the PFS of patients with osteosarcoma,and can be used as an important reference index for the prognosis of patients with osteosarcoma.At the same time,the effective prognostic nomogram based on direct bilirubin can provide more accurate prognostic prediction for patients with osteosarcoma.