Study On UPSA In Early Diagnosis And The Role Of PTTG1 In Prostate Cancer Progression

Background: Prostate Cancer(PCa)is the most common cancer in men.Among the new global cancer statistics,in 2018,there are 1,276,106(7.1%)men diagonosis with prostate cancer,accounting for the third place in new-onset tumors.In Western countries,prostate cancer is in the first place of cancer incidence in men and the second most common malignant tumor.In recent years,the incidence of prostate cancer in China has shown a clear upward trend.Ranked 6th in the incidence of male malignant tumors,and its rate of disease onset ranks first in the past decade;and there is a significant difference in prostate cancer patients in China compared with Western countries.In 2013,patients with newly diagnosed prostate cancer in China,the proportion of middle-and late-stage patients was higher(58.1%),which is in a larger amount in China.Prostate cancer has become a malignant disease that seriously threatens the health and life of men in China.Therefore,effective improvement of prostate cancer prevention and treatment can be working out in two aspects,on the one hand to enhance the effectiveness of early diagnosis,early detection and early diagnosis;on the other hand,to optimize the diagnosis strategy of advanced prostate cancer,improve patient quality of life and prolong survival time.For the early diagnosis of prostate cancer,as with other malignant tumors,finding suitable early diagnostic biomarkers is an effective method to improve the comprehensive efficacy of the disease.For the widespread use of PSA screening in clinical practice,the sensitivity of PSA is not high.Excessive treatment for patients,resulting in the economic burden.Therefore,finding new markers for early diagnosis of prostate cancer,while reducing unnecessary prostate biopsy,while preventing excessive prostate cancer treatment,as well as non-invasive detection,will be an ideal biomarker for clinical diagnosis of prostate cancer.On the other hand,among the newly diagnosed patients with prostate cancer in China,the proportion of patients with moderate to high risk accounts for the majority.Metastatic castration-resistant prostate cancer(m CRPC)is the leading cause of death in patients.To study the mechanism of tumor development and development,to explore the mechanism of tumor proliferation and invasion,and to find specific drugs for tumor targeting molecules.These are difficult and important in the research of clinical prostate cancer.Purpose: To improve the early diagnosis efficiency of prostate cancer,reduce unnecessary prostate cancer biopsy,avoid over-diagnosis and reduce the economic burden of patients.At the same time,we use NGS technology to find possible key molecules for prostate cancer development,focus on its molecular biological function,and clarify its role in the malignant progression of prostate cancer,drug resistance mechanism,and oncology-related features.Tumor big data personalization and precision treatment of heroes must be based.Methods: We collected a total of 447 urine samples from patients who underwent prostate biopsy in our hospital from June 2015 to December 2016.The urine PSA values were measured by chemical immunoluminescence and were based on clinical relevant information and pathological confirmation;explore the clinical value of urine PSA in the early diagnosis of prostate cancer.At the same time,we analyzed the big data of Chinese prostate cancer transcriptomics in the previous public database,and selected relevant data to identify important molecules related to the development of prostate cancer.Molecular biological function tests are performing on the sieved molecules,and bioinformatics methods are using to explore upstream and downstream molecules that may interact.Western blotting was using to detect the expression of PTTG1 in different prostate cancer cell lines.The expression of PTTG1 was detected by q RT-PCR.The expression of PTTG1 was observed to express the proliferation of prostate cancer cells.The change of invasion ability and migration ability were observed.Variety.The expression of PTTG1 was knocked down by Si RNA,and changes in proliferation ability,invasion ability,and migration ability of prostate cancer cells were observed.By tumor tissue microarray analysis PTTG1 molecules may interrelated and associated with the use of PARP inhibitors olaparib application,PTTG1 observed expression changes and related molecules of proven possible downstream relationship and mechanism of action.Results: The first part of the early diagnosis of prostate cancer preliminary exploration and verification of the clinical diagnostic value of PSA,and the expression of urine PSA in the EPS urine in prostate biopsy patients.It was found that the level of urine PSA hematuria ratio can effectively distinguish between PCa and BPH patients,especially in the traditional prostate cancer diagnostic gray area(PSA4-10ng/ml),and the Chinese population prostate cancer diagnosis gray area(PSA4-20ng/ml).Compared with serum PSA and PSA free ratio,it has better diagnostic efficiency,which is convenient for guiding the rapid judgment of clinical prostate biopsy.The second and third parts of the study confirmed that PTTG1 can promote prostate cancer cells' proliferation,migration and invasion both in vivo experiments and in vitro cell cytology experiments.Further explore the biological mechanism and molecular signaling pathways that PTTG1 may interact.In the treatment of xenograft model,we found that the PARP inhibitor olaparib combined with carboplatin could significantly inhibit the expression of PTTG1 and inhibit the proliferation of prostate cancer cells.At the same time,we found that the signal of PTTG1 might be involved in microarray detection,may interact with FOXM1/PLK1-DDR path.By knocking down FOXM1 and PLK1,we found that PTTG1 is a direct downstream target gene of FOXM1,and PLK1 and FOXM1 can interact through the level of phosphorylation.Therefore,DDR-PLK1/FOXM1-PTTG1 may promote the invasion and metastasis of prostate cancer by regulating the genes through the transcription layer.Conclusion: Urine-based PSA can be used as a non-invasive liquid biopsy;PSA hematuria ratio can help diagnosis prostate cancer,especially in the traditional diagnostic gray area of prostate cancer(PSA 4-10 ng / ml)and PSA diagnostic gray area in Chinese population(4-20ng/ml)patients who were leading to ungo unnecessary biopsy.The study of PTTG1 in the progression of prostate cancer proves that it is a key molecule in the development of prostate cancer.DDR-PLK1/FOXM1-PTTG1 promotes prostate cancer migration,invasion and metastasis through the regulation of genes in the transcription layer,and clarifies its malignant progression in prostate cancer.The mechanism of drug resistance and the role of oncology-related features of this signal pathway can provide a basis for the future treatment of adult big data with precise and precise treatment of heroes.