Correlation Of Some Risk Factors For Bone Metastasis In The Initially Diagnosed Prostate Cancer Patients

BackgroundCircular RNA can be used as proto oncogene and tumor suppressor gene in tumor cell metastasis.The current study found that hsa_circ₀075542 was down regulated in prostate cancer（PCa）,but its mechanism of regulating PCa cell invasion,migration and apoptosis is unclear.At the same time,there are many risk factors for PCa bone metastasis.Whether circular RNA,serum markers,specific location and quantity of bone metastasis and total prostate volume of initially diagnosed prostate cancer patients are risk factors for bone metastasis need further verification,and the differences of confirmed risk factors in different Gleason ISUP groups also need to be clarified.Therefore,this study aims to explore hsa_circ₀075542 is the mechanism of regulating PCa cell metastasis,serum markers in different Gleason ISUP groups,the specific location and quantity of bone metastasis and the total volume of prostate at the initial diagnosis a risk factor for bone metastasis in patients with PCa at the initial diagnosis?So as to better guide clinical work.MethodsIn the first part of this study,LNCaP cells and PC3 cells were used to transfect hsa_circ₀075542,CO transfected miR-1197 and plasmid were used for functional verification,and WB experiment was carried out to detect the expression level of target gene hoxc11.In the second part of this study to the fourth collected the clinical data of initially diagnosed PCa patients from January 2012 to June 2020 were collected..The data came from Shenzhen Hospital,Zhujiang Hospital of Southern Medical University,the Third Hospital of Sun Yat sen University and Yuebei People’s Hospital Affiliated to Medical College of Shantou University.All patients were diagnosed according to the Gleason grading system of the international society of urological pathology（ISUP）.Serum PSA,ALP,TNM stage,specific number and site of bone metastasis,total prostate volume and the time of progression to CRPC after ADT treatment was recorded.The effects of serum markers,specific number and location of bone metastasis and total prostate volume on the time of progression to CRPC in Gleason ISUP group were statistically analyzed.ResultsCompared with adjacent tissues,The hsa_circ₀075542 level decreased by about 75%.Overexpression vector of hsa_circ₀075542,the viability,migration,invasiveness and apoptosis rate of prostate cancer cells were significantly different from those of empty vector group（P<0.05）.There was significant difference in the level of HOXC11 between LNCaP and PC3 cells transfected with miR-1197 mimic plus ov_circ₀075542（P<0.05）.The ALP of Gleason ISUP 4 and 5 groups and PSA of ISUP 3,4 and 5 groups were statistically significant（P<0.001）.Nomogram model showed that TNM stage had the greatest impact on PFS,followed by Gleason ISUP,TPSA and ALP.Cox analysis:Gleason grade,TPSA,ALP,TNM stage,number of bone metastases and total prostate volume were all related to PFS（P<0.05）.Kaplan Meier analysis:Patients with PCa with high Gleason grade,high tPSA or ALP level or advanced TNM stage had worse PFS（P<0.05）.The nomogram model showed that TNM staging had the greatest impact on PFS,followed by Gleason grading,TPSA and ALP.The risk of developing CRPC increased significantly with the increase of the number of bone metastases（P<0.001）.There was no significant difference among different metastatic sites（P=0.065）.Similar results were obtained under different treatment regimens.PFS was shorter in patients with total prostate volume>60ml,T stage≥3 and initial diagnosis with bone metastasis（P<0.01）.ConclusionHsa_circ₀075542 acts as a sponge for Mir-1197 and up-regulates HOXC11 to inhibit PCa cell metastasis.Serum ALP in ISUP≥ 4 group and PSA in ISUP≥ 3 group were significantly increased,and the established nomogram model could accurately predict patients’ PFS.The number of bone metastases in initially diagnosed PCa patients was more closely related to the time of progression to CRPC than the location.PFS was shorter in patients with total prostate volume>60ml,T stage≥3,and bone metastasis in initially diagnosed.Gleason grade,tPSA,ALP,TNM,the number of bone metastasis and the total prostate volume were risk factors for bone metastases in patients with PCa at the initial diagnosis.However,overexpression of hsa_circ₀075542 and the site of bone metastasis were not.