SETDB1 has been established as an oncogene in a number of human carcinomas. The present study was to evaluate the expression of SETDB1 in prostate cancer (PCa) tissues and cells and to preliminarily investigate the ...SETDB1 has been established as an oncogene in a number of human carcinomas. The present study was to evaluate the expression of SETDB1 in prostate cancer (PCa) tissues and cells and to preliminarily investigate the role of SETDB1 in prostate tumorigenesis in vitro. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to detect the expression of SETDB1 in PCa tissues, adjacent normal tissues, benign prostatic hyperplasia (BPH) tissues, PCa cell lines and normal prostate epithelial cells. The results suggested that SETDB1 was upregulated in human PCa tissues compared with normal tissues at the mRNA and protein levels. The role of SETDB1 in proliferation was analyzed with cell counting kit-8, colony-forming efficiency and flow cytometry assays. The results indicated that downregulation of SETDB1 by siRNA inhibited PCa cell growth, and induced GO/G1 cell cycle arrest. The PCa cell migration and invasion decreased by silcencing SETDBt which were assessed by using in vitro scratch and transwell invasion assay respectively. Our data suggested that SETDB1 is overexpressed in human PCa. Silencing SETDB1 inhibited PCa cell proliferation, migration and invasion.展开更多
Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml^-1, however, it remains controversial whether %fPSA is...Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml^-1, however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml^-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA〉4.0 ng ml^-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1.展开更多
We performed this study to investigate the diagnostic performance of prostate-specific antigen density(PSAD)in a multicenter cohort of the Chinese Prostate Cancer Consortium.Outpatients with prostate-specific antigen(...We performed this study to investigate the diagnostic performance of prostate-specific antigen density(PSAD)in a multicenter cohort of the Chinese Prostate Cancer Consortium.Outpatients with prostate-specific antigen(PSA)levels≥4.0 ng ml^(-1) regardless of digital rectal examination(DRE)results or PSA levels<4.0 ng ml^(-1)and abnormal DRE results were included from 18 large referral hospitals in China.The diagnostic performance of PSAD and the sensitivity and specificity for the diagnosis of prostate cancer(PCa)and high-grade prostate cancer(HGPCa)at different cutoff values were evaluated.A total of 5220 patients were included in the study,and 2014(38.6%)of them were diagnosed with PCa.In patients with PSA levels ranging from 4.0 to 10.0 ng ml^(-1),PSAD was associated with PCa and HGPCa in both univariate(odds ratio[OR]=45.15,P<0.0001 and OR=25.38,P<0.0001,respectively)and multivariate analyses(OR=52.55,P<0.0001 and OR=26.05,P<0.0001,respectively).The areas under the receiver operating characteristic curves(AUCs)of PSAD in predicting PCa and HGPCa were 0.627 and 0.630,respectively.With the PSAD cutoff of 0.10 ng ml^(-2),we obtained a sensitivity of 88.7%for PCa,and nearly all(89.9%)HGPCa cases could be detected and biopsies could be avoided in 20.2%of the patients(359/1776 cases).Among these patients who avoided biopsies,only 30 cases had HGPCa.We recommend 0.10 ng ml^(-2) as the proper cutoff value of PSAD,which will obtain a sensitivity of nearly 90%for both PCa and HGPCa.The results of this study should be validated in prospective,population-based multicenter studies.展开更多
Prostate cancer antigen 3 (PCA3) is a biomarker for diagnosing prostate cancer (PCa) identified in the Caucasian population. We evaluated the effectiveness of urinary PCA3 in predicting the biopsy result in 500 me...Prostate cancer antigen 3 (PCA3) is a biomarker for diagnosing prostate cancer (PCa) identified in the Caucasian population. We evaluated the effectiveness of urinary PCA3 in predicting the biopsy result in 500 men undergoing initial prostate biopsy. The predictive power of the PCA3 score was evaluated by the area under receiver operating characteristic (ROC) curve (AUC) and by decision curve analysis. PCA3 score sufficed to discriminate positive from negative prostate biopsy results but was not correlated with the aggressiveness of PCa. The ROC analysis showed a higher AUC for the PCA3 score than %fPSA (0.750 vs 0.622, P = 0.046) in patients with a PSA of 4.0-10.0 ng ml-I, but the PCA3-based model is not significantly better than the base model. Decision curve analysis indicates the PCA3-based model was superior to the base model with a higher net benefit for almost all threshold probabilities, especially the threshold probabilities of 25%-40% in patients with a PSA of 4.0-10.0 ng ml-1. However, the AUC of the PCA3 score (0.712) is not superior to %fPSA (0.698) or PSAD (0.773) in patients with a PSA 〉10.0 ng ml-1. Our results confirmed that the RT-PCR-based PCA3 test moderately improved diagnostic accuracy in Chinese patients undergoing first prostate biopsy with a PSA of 4.0-10.0 ng ml-1.展开更多
Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog(TMPRSS2-ERG fusion)is a common genetic alteration in prostate cancer among Western populations and has been sugg...Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog(TMPRSS2-ERG fusion)is a common genetic alteration in prostate cancer among Western populations and has been suggested as playing a role in tumorigenesis and progression of prostate cancer.However,the prevalence of TMPRSS2-ERG fusion differs among different ethnic groups,and contradictory results have been reported in Asian patients.We aim to evaluate the prevalence and significance of TMPRSS2-ERG fusion as a molecular subtyping and prognosis indicator of prostate cancer in Asians.We identified the fusion status in 669 samples from prostate biopsy and radical prostatectomy by fluorescence in situ hybridization and/or immunohistochemistry in China.We examined the association of TMPRSS2-ERG fusion with clinicopathological characteristics and biochemical recurrence by Chi-square test and Kaplan–Meier analysis.Finally,a systematic review was performed to investigate the positive rate of the fusion in Asian prostate cancer patients.McNemar’s test was employed to compare the positive rates of TMPRSS2-ERG fusion detected using different methods.The positive rates of TMPRSS2-ERG fusion were 16%in our samples and 27%in Asian patients.In our samples,9.4%and 19.3%of cases were recognized as fusion positive by fluorescence in situ hybridization and immunohistochemistry,respectively.No significant association between the fusion and clinical parameters was observed.TMPRSS2-ERG fusion is not a frequent genomic alteration among Asian prostate cancer patients and has limited significance in clinical practices in China.Besides ethnic difference,detection methods potentially influence the results showing a positive rate of TMPRSS2-ERG fusion.展开更多
Membrane-associated guanylate kinase(MAGUK)family protein MAGUK invert 2(MAGI-2)has been demonstrated to be involved in the tumorigenic mechanism of prostate cancer.The objective of this study was to investigate the e...Membrane-associated guanylate kinase(MAGUK)family protein MAGUK invert 2(MAGI-2)has been demonstrated to be involved in the tumorigenic mechanism of prostate cancer.The objective of this study was to investigate the expression of MAGI・2 at mRNA and protein levels.The prog no stic value of MAGI-2 in Han Chin ese patie nts with prostate cancer was also investigated.The expression data of MAGI・2 were assessed through database retrieval,analysis of sequencing data from our group,and tissue immunohistochemistry using digital scoring system(H・score).The clinical,pathological,and follow-up data were collected.The expression of MAGI-2 in prostate tumor tissues and prostate normal tissues was evaluated and compared.MAGI-2 expression was associated with clinical parameters including tumor stage,lymph node status,Gleason score,PSA level,and biochemical recurrenee of prostate cancer.The relative expression of MAGI-2 mRNA was lower in the tumor tissue in The Cancer Genome Atlas(TCGA)database and sequencing data(P<0.001).There was no difference in MAGI-2 protein expression between tumor and normal tissues in tissue microarray(TMA)results.MAGI-2 expression was associated with pathological tumor stage(P=0.02),Gleason score(P=0.05),and preoperation prostate-specific antigen(PSA;P=0.04).A positive correlation was identified between MAGI-2 and phosphatase and tensin homolog deleted on chromosome 10(PTEN)expressions through the analysis of TCGA and TMA data(P<0.0001).Patients with higher MAGI-2 expression had longer biochemical recurrence-free survival in the univariate analysis(P=0.005),which in dicates an optimal prog no stic value of MAGI-2 in Han Chin ese patie nts with prostate can cer.I n con elusion,MAGI-2 expressi on gradually decreases with tumor progression,and can be used as a predictor of tumor recurrence in Chinese patients.展开更多
基金This study was supported by the National Basic Research Program of China (No. 2012CB518306), the National Natural Science Foundation of China (No. 81101946), the Prostate Cancer Foundation Young Investigator Award and the Shanghai Pujiang Program (No. 12PID008).
文摘SETDB1 has been established as an oncogene in a number of human carcinomas. The present study was to evaluate the expression of SETDB1 in prostate cancer (PCa) tissues and cells and to preliminarily investigate the role of SETDB1 in prostate tumorigenesis in vitro. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to detect the expression of SETDB1 in PCa tissues, adjacent normal tissues, benign prostatic hyperplasia (BPH) tissues, PCa cell lines and normal prostate epithelial cells. The results suggested that SETDB1 was upregulated in human PCa tissues compared with normal tissues at the mRNA and protein levels. The role of SETDB1 in proliferation was analyzed with cell counting kit-8, colony-forming efficiency and flow cytometry assays. The results indicated that downregulation of SETDB1 by siRNA inhibited PCa cell growth, and induced GO/G1 cell cycle arrest. The PCa cell migration and invasion decreased by silcencing SETDBt which were assessed by using in vitro scratch and transwell invasion assay respectively. Our data suggested that SETDB1 is overexpressed in human PCa. Silencing SETDB1 inhibited PCa cell proliferation, migration and invasion.
文摘Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml^-1, however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml^-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA〉4.0 ng ml^-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1.
基金for National Natural Science Foundation Youth Project(No.81702514 to RC).
文摘We performed this study to investigate the diagnostic performance of prostate-specific antigen density(PSAD)in a multicenter cohort of the Chinese Prostate Cancer Consortium.Outpatients with prostate-specific antigen(PSA)levels≥4.0 ng ml^(-1) regardless of digital rectal examination(DRE)results or PSA levels<4.0 ng ml^(-1)and abnormal DRE results were included from 18 large referral hospitals in China.The diagnostic performance of PSAD and the sensitivity and specificity for the diagnosis of prostate cancer(PCa)and high-grade prostate cancer(HGPCa)at different cutoff values were evaluated.A total of 5220 patients were included in the study,and 2014(38.6%)of them were diagnosed with PCa.In patients with PSA levels ranging from 4.0 to 10.0 ng ml^(-1),PSAD was associated with PCa and HGPCa in both univariate(odds ratio[OR]=45.15,P<0.0001 and OR=25.38,P<0.0001,respectively)and multivariate analyses(OR=52.55,P<0.0001 and OR=26.05,P<0.0001,respectively).The areas under the receiver operating characteristic curves(AUCs)of PSAD in predicting PCa and HGPCa were 0.627 and 0.630,respectively.With the PSAD cutoff of 0.10 ng ml^(-2),we obtained a sensitivity of 88.7%for PCa,and nearly all(89.9%)HGPCa cases could be detected and biopsies could be avoided in 20.2%of the patients(359/1776 cases).Among these patients who avoided biopsies,only 30 cases had HGPCa.We recommend 0.10 ng ml^(-2) as the proper cutoff value of PSAD,which will obtain a sensitivity of nearly 90%for both PCa and HGPCa.The results of this study should be validated in prospective,population-based multicenter studies.
文摘Prostate cancer antigen 3 (PCA3) is a biomarker for diagnosing prostate cancer (PCa) identified in the Caucasian population. We evaluated the effectiveness of urinary PCA3 in predicting the biopsy result in 500 men undergoing initial prostate biopsy. The predictive power of the PCA3 score was evaluated by the area under receiver operating characteristic (ROC) curve (AUC) and by decision curve analysis. PCA3 score sufficed to discriminate positive from negative prostate biopsy results but was not correlated with the aggressiveness of PCa. The ROC analysis showed a higher AUC for the PCA3 score than %fPSA (0.750 vs 0.622, P = 0.046) in patients with a PSA of 4.0-10.0 ng ml-I, but the PCA3-based model is not significantly better than the base model. Decision curve analysis indicates the PCA3-based model was superior to the base model with a higher net benefit for almost all threshold probabilities, especially the threshold probabilities of 25%-40% in patients with a PSA of 4.0-10.0 ng ml-1. However, the AUC of the PCA3 score (0.712) is not superior to %fPSA (0.698) or PSAD (0.773) in patients with a PSA 〉10.0 ng ml-1. Our results confirmed that the RT-PCR-based PCA3 test moderately improved diagnostic accuracy in Chinese patients undergoing first prostate biopsy with a PSA of 4.0-10.0 ng ml-1.
基金This research was funded by the National Nature Science Foundation Youth Project(Grant No.81702514)the National Natural Science Foundation of China(Grant No.81430058)the Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning(Grant No.20184Y0130).
文摘Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog(TMPRSS2-ERG fusion)is a common genetic alteration in prostate cancer among Western populations and has been suggested as playing a role in tumorigenesis and progression of prostate cancer.However,the prevalence of TMPRSS2-ERG fusion differs among different ethnic groups,and contradictory results have been reported in Asian patients.We aim to evaluate the prevalence and significance of TMPRSS2-ERG fusion as a molecular subtyping and prognosis indicator of prostate cancer in Asians.We identified the fusion status in 669 samples from prostate biopsy and radical prostatectomy by fluorescence in situ hybridization and/or immunohistochemistry in China.We examined the association of TMPRSS2-ERG fusion with clinicopathological characteristics and biochemical recurrence by Chi-square test and Kaplan–Meier analysis.Finally,a systematic review was performed to investigate the positive rate of the fusion in Asian prostate cancer patients.McNemar’s test was employed to compare the positive rates of TMPRSS2-ERG fusion detected using different methods.The positive rates of TMPRSS2-ERG fusion were 16%in our samples and 27%in Asian patients.In our samples,9.4%and 19.3%of cases were recognized as fusion positive by fluorescence in situ hybridization and immunohistochemistry,respectively.No significant association between the fusion and clinical parameters was observed.TMPRSS2-ERG fusion is not a frequent genomic alteration among Asian prostate cancer patients and has limited significance in clinical practices in China.Besides ethnic difference,detection methods potentially influence the results showing a positive rate of TMPRSS2-ERG fusion.
基金The authors acknowledge the contribution of Dr.Lin Zhao,Dr.Ya-Sheng Zhu,Dr.Zhe-Xu Cao,and Dr.Chen Ye from the Department of Urology,Changhai Hospital,Naval Medical University(the Second Military Medical University),for their kind help during the experimental process.This study was supported by the National Natural Science Foundation of China(No.81430058)Shanghai Key Laboratory of Cell Engineering(No.14DZ2272300).
文摘Membrane-associated guanylate kinase(MAGUK)family protein MAGUK invert 2(MAGI-2)has been demonstrated to be involved in the tumorigenic mechanism of prostate cancer.The objective of this study was to investigate the expression of MAGI・2 at mRNA and protein levels.The prog no stic value of MAGI-2 in Han Chin ese patie nts with prostate cancer was also investigated.The expression data of MAGI・2 were assessed through database retrieval,analysis of sequencing data from our group,and tissue immunohistochemistry using digital scoring system(H・score).The clinical,pathological,and follow-up data were collected.The expression of MAGI-2 in prostate tumor tissues and prostate normal tissues was evaluated and compared.MAGI-2 expression was associated with clinical parameters including tumor stage,lymph node status,Gleason score,PSA level,and biochemical recurrenee of prostate cancer.The relative expression of MAGI-2 mRNA was lower in the tumor tissue in The Cancer Genome Atlas(TCGA)database and sequencing data(P<0.001).There was no difference in MAGI-2 protein expression between tumor and normal tissues in tissue microarray(TMA)results.MAGI-2 expression was associated with pathological tumor stage(P=0.02),Gleason score(P=0.05),and preoperation prostate-specific antigen(PSA;P=0.04).A positive correlation was identified between MAGI-2 and phosphatase and tensin homolog deleted on chromosome 10(PTEN)expressions through the analysis of TCGA and TMA data(P<0.0001).Patients with higher MAGI-2 expression had longer biochemical recurrence-free survival in the univariate analysis(P=0.005),which in dicates an optimal prog no stic value of MAGI-2 in Han Chin ese patie nts with prostate can cer.I n con elusion,MAGI-2 expressi on gradually decreases with tumor progression,and can be used as a predictor of tumor recurrence in Chinese patients.