The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by l...The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by low predictive potential and inability to predict which patients are at risk of developing metastatic disease. The aim of this study is to investigate the exon 4 of the KLK2 gene of subjects for changes in its nucleotide sequences (SNPs) and determine the correlation of these changes with serum PSA in an Igbo population of Nigeria. One hundred male subjects aged 40 years and above, who gave their consent, were used for the study. Their PSA determinations were done using ELISA technique while genetic studies were carried out using real-time PCR. tPSA, fPSA, and % fPSA of the subjects ranged between 0.8% - 18.30%, 0.10% - 1.60% and 0.0% - 0.7% respectively. Of the 100 subjects, 28 subjects had tPSA levels above 4.0 ng/ml with a mean of 7.10 (±3.30) ng/ml. Those with tPSA less than 4 ng/ml had a mean of 1.87 (±0.85) ng/m. 15 subjects showed SNPs with a mean tPSA of 6.87 (±4.82) ng/ml while the remaining 85 subjects without SNPs had a mean of 1.86 (±0.80) ng/ml. Results from direct DNA sequencing showed 11 SNPs. Ten subjects are curated in SNP database while one is uncurated. The Chi-square test showed significant association (p = 0.00) between tPSA levels and SNPs mutation (X<sup>2</sup> = 17.35, p = 0.00). A Kruskal-Wallis test demonstrated that the positional arrangement of the SNP mutations had no effect on PSA-total or free-values (H (10) = 10.92, p = 0.28;H (10) = 10.07, p = 0.38 respectively). Two SNPs: rs6072 and rs74478031 were associated with elevated PSA levels (p < 0.05). Their presence, therefore, has the potential to serve, in conjunction with raised PSA, as biomarkers of prostate cancer in the study population.展开更多
目的探讨前2肽前列腺特异性抗原(isoform[-2]prostate specific antigen,p2PSA)及前列腺健康指数(prostate health index,PHI)早期诊断前列腺癌的临床价值。方法选择2019年11月至2021年2月在昆明医科大学第二附属医院住院治疗并拟首次...目的探讨前2肽前列腺特异性抗原(isoform[-2]prostate specific antigen,p2PSA)及前列腺健康指数(prostate health index,PHI)早期诊断前列腺癌的临床价值。方法选择2019年11月至2021年2月在昆明医科大学第二附属医院住院治疗并拟首次接受经超声引导下前列腺穿刺活检或手术切除的103例患者,根据病理结果分为前列腺癌组(45例)与前列腺良性疾病组(以下简称良性疾病组,58例),选择同期健康体检的43例健康男性作为健康对照组,进行各项血清学指标检测。根据总前列腺特异性抗原(total prostate specific antigen,tPSA)检测结果将146例研究对象分为tPSA≤10ng/ml组与tPSA>10ng/ml组,每组再各分出前列腺癌亚组与非前列腺癌亚组。计算游离/总前列腺特异性抗原(free/total prostate specific antigen,f/tPSA)和PHI。比较各项指标差异,用受试者工作特征(receiver operating characteristic,ROC)曲线评价不同分组中各项指标诊断前列腺癌的效能。结果前列腺癌组血清tPSA、游离前列腺特异性抗原(free prostate specific antigen,fPSA)、p2PSA水平及PHI均明显高于良性疾病组及健康对照组,而f/tPSA则相反,差异均有显著性(P<0.05)。PHI的曲线下面积最大(0.89,0.95),提示其诊断效能最佳。结论PHI是一个敏感度、特异度均较高且不受tPSA水平局限的优秀指标,而p2PSA相比之下优势不明显。PHI有望成为前列腺癌早期诊断的最佳指标。展开更多
To assure what sequence associated with the androgen regulation, a 15 bp region at the upstream of the ARE of prostate-specific antigen (PSA) promoter, termed RFA, was found in-dispensable for androgen receptor (AR)-m...To assure what sequence associated with the androgen regulation, a 15 bp region at the upstream of the ARE of prostate-specific antigen (PSA) promoter, termed RFA, was found in-dispensable for androgen receptor (AR)-mediated transactivation of PSA promoter. In transfection and CAT assays, some nucleotides substitution in RFA could significantly decrease the androgen inducibility for PSA promoter. The in vitro DNA binding assay demonstrated that RFA bound spe-cifically with some non-receptor protein factors in prostate cell nucleus, but the mutant type of RFA lost this ability, so RFA might be a novel accessory cis-element. The RFA-binding proteins were isolated and purified by affinity chromatography using RFA probes. SDS-PAGE and preliminary protein identification showed these proteins possessed sequence high homology with multifunc-tional protein heterogeneous nuclear ribonucleoprotein A1, A2 (hnRNP A1, A2). RFA-binding pro-teins possibly cooperate with AR-mediated transactivation for PSA promoter as coactivator. The study results will facilitate further understanding the mechanism and tissue specificity of PSA pro-moter.展开更多
Prostate cancer （PCa） is one of the most common cancers among men globally. The authors aimed to evaluate the ability of the Prostate Imaging Reporting and Data System version 2 （PI-RADS v2） to classify men with P...Prostate cancer （PCa） is one of the most common cancers among men globally. The authors aimed to evaluate the ability of the Prostate Imaging Reporting and Data System version 2 （PI-RADS v2） to classify men with PCa, clinically significant PCa （CSPCa）, or no PCa, especially among those with serum total prostate-specific antigen （tPSA） levels in the ＂gray zone＂ （4-10 ng ml-1）. A total of 308 patients （355 lesions） were enrolled in this study. Diagnostic efficiency was determined. Univariate and multivariate analyses, receiver operating characteristic curve analysis, and decision curve analysis were performed to determine and compare the predictors of PCa and CSPCa. The results suggested that PI-RADS v2, tPSA, and prostate-specific antigen density （PSAD） were independent predictors of PCa and CSPCa. A PI-RADS v2 score L≥4 provided high negative predictive values （91.39% for PCa and 95.69% for CSPCa）. A model of PI-RADS combined with PSA and PSAD helped to define a high-risk group （PI-RADS score = 5 and PSAD L≥0 15 ng ml-1 cm-3, with tPSA in the gray zone, or PI-RADS score L≥4 with high tPSA level） with a detection rate of 96.1% for PCa and 93.0% for CSPCa while a low-risk group with a detection rate of 6.1% for PCa and 2.2% for CSPCa. It was concluded that the PI-RADS v2 could be used as a reliable and independent predictor of PCa and CSPCa. The combination of PI-RADS v2 score with PSA and PSAD could be helpful in the prediction and diagnosis of PCa and CSPCa and, thus, may help in preventing unnecessary invasive procedures.展开更多
The [-2]proPSA （p2PSA） and its derivatives, the p2PSA-to-free PSA ratio （%p2PSA）, and the Prostate Health Index （PHI） have greatly improved discrimination between men with and without prostate cancer （PCa） in ...The [-2]proPSA （p2PSA） and its derivatives, the p2PSA-to-free PSA ratio （%p2PSA）, and the Prostate Health Index （PHI） have greatly improved discrimination between men with and without prostate cancer （PCa） in prostate biopsies. However, little is known about their performance in cases where a digital rectal examination （DRE） and transrectal ultrasonography （TRUS） are negative. A prospective cohort of 261 consecutive patients in China with negative DRE and TRUS were recruited and underwent prostate biopsies. A serum sample had collected before the biopsy was used to measure various PSA derivatives, including total prostate-specific antigen （tPSA）, free PSA, and p2PSA. For each patient, the free-to-total PSA ratio （%fPSA）, PSA density （PSAD）, p2PSA-to-free PSA ratio （%p2PSA）, and PHI were calculated. Discriminative performance was assessed using the area under the receiver operating characteristic curve （AUC） and the biopsy rate at 91% sensitivity. The AUC scores within the entire cohort with respect to age, tPSA, %fPSA, PSAD, p2PSA, %p2PSA, and PHI were 0.598, 0.751, 0.646, 0.789, 0.814, 0.808, and 0.853, respectively. PHI was the best predictor of prostate biopsy results, especially in patients with a tPSA of 10.1-20 ng ml-1. Compared with other markers, at a sensitivity of 91%, PHI was the most useful for determining which men did not need to undergo biopsy, thereby avoiding unnecessary procedures. The use of PHI could improve the accuracy of PCa detection by predicting prostate biopsy outcomes among men with a negative DRE and TRUS in China.展开更多
Diabetes mellitus （DM） is a considerably common public health problem, which is associated with severecomplications. In China, considerably increasing people are diagnosed as DM each year. It has been reported that ...Diabetes mellitus （DM） is a considerably common public health problem, which is associated with severecomplications. In China, considerably increasing people are diagnosed as DM each year. It has been reported that DM has an increased risk of several neoplasm, notably cancer of the pancreatic, liver, breast, bladder and colon.1 However,展开更多
文摘The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by low predictive potential and inability to predict which patients are at risk of developing metastatic disease. The aim of this study is to investigate the exon 4 of the KLK2 gene of subjects for changes in its nucleotide sequences (SNPs) and determine the correlation of these changes with serum PSA in an Igbo population of Nigeria. One hundred male subjects aged 40 years and above, who gave their consent, were used for the study. Their PSA determinations were done using ELISA technique while genetic studies were carried out using real-time PCR. tPSA, fPSA, and % fPSA of the subjects ranged between 0.8% - 18.30%, 0.10% - 1.60% and 0.0% - 0.7% respectively. Of the 100 subjects, 28 subjects had tPSA levels above 4.0 ng/ml with a mean of 7.10 (±3.30) ng/ml. Those with tPSA less than 4 ng/ml had a mean of 1.87 (±0.85) ng/m. 15 subjects showed SNPs with a mean tPSA of 6.87 (±4.82) ng/ml while the remaining 85 subjects without SNPs had a mean of 1.86 (±0.80) ng/ml. Results from direct DNA sequencing showed 11 SNPs. Ten subjects are curated in SNP database while one is uncurated. The Chi-square test showed significant association (p = 0.00) between tPSA levels and SNPs mutation (X<sup>2</sup> = 17.35, p = 0.00). A Kruskal-Wallis test demonstrated that the positional arrangement of the SNP mutations had no effect on PSA-total or free-values (H (10) = 10.92, p = 0.28;H (10) = 10.07, p = 0.38 respectively). Two SNPs: rs6072 and rs74478031 were associated with elevated PSA levels (p < 0.05). Their presence, therefore, has the potential to serve, in conjunction with raised PSA, as biomarkers of prostate cancer in the study population.
文摘目的探讨前2肽前列腺特异性抗原(isoform[-2]prostate specific antigen,p2PSA)及前列腺健康指数(prostate health index,PHI)早期诊断前列腺癌的临床价值。方法选择2019年11月至2021年2月在昆明医科大学第二附属医院住院治疗并拟首次接受经超声引导下前列腺穿刺活检或手术切除的103例患者,根据病理结果分为前列腺癌组(45例)与前列腺良性疾病组(以下简称良性疾病组,58例),选择同期健康体检的43例健康男性作为健康对照组,进行各项血清学指标检测。根据总前列腺特异性抗原(total prostate specific antigen,tPSA)检测结果将146例研究对象分为tPSA≤10ng/ml组与tPSA>10ng/ml组,每组再各分出前列腺癌亚组与非前列腺癌亚组。计算游离/总前列腺特异性抗原(free/total prostate specific antigen,f/tPSA)和PHI。比较各项指标差异,用受试者工作特征(receiver operating characteristic,ROC)曲线评价不同分组中各项指标诊断前列腺癌的效能。结果前列腺癌组血清tPSA、游离前列腺特异性抗原(free prostate specific antigen,fPSA)、p2PSA水平及PHI均明显高于良性疾病组及健康对照组,而f/tPSA则相反,差异均有显著性(P<0.05)。PHI的曲线下面积最大(0.89,0.95),提示其诊断效能最佳。结论PHI是一个敏感度、特异度均较高且不受tPSA水平局限的优秀指标,而p2PSA相比之下优势不明显。PHI有望成为前列腺癌早期诊断的最佳指标。
文摘To assure what sequence associated with the androgen regulation, a 15 bp region at the upstream of the ARE of prostate-specific antigen (PSA) promoter, termed RFA, was found in-dispensable for androgen receptor (AR)-mediated transactivation of PSA promoter. In transfection and CAT assays, some nucleotides substitution in RFA could significantly decrease the androgen inducibility for PSA promoter. The in vitro DNA binding assay demonstrated that RFA bound spe-cifically with some non-receptor protein factors in prostate cell nucleus, but the mutant type of RFA lost this ability, so RFA might be a novel accessory cis-element. The RFA-binding proteins were isolated and purified by affinity chromatography using RFA probes. SDS-PAGE and preliminary protein identification showed these proteins possessed sequence high homology with multifunc-tional protein heterogeneous nuclear ribonucleoprotein A1, A2 (hnRNP A1, A2). RFA-binding pro-teins possibly cooperate with AR-mediated transactivation for PSA promoter as coactivator. The study results will facilitate further understanding the mechanism and tissue specificity of PSA pro-moter.
文摘Prostate cancer （PCa） is one of the most common cancers among men globally. The authors aimed to evaluate the ability of the Prostate Imaging Reporting and Data System version 2 （PI-RADS v2） to classify men with PCa, clinically significant PCa （CSPCa）, or no PCa, especially among those with serum total prostate-specific antigen （tPSA） levels in the ＂gray zone＂ （4-10 ng ml-1）. A total of 308 patients （355 lesions） were enrolled in this study. Diagnostic efficiency was determined. Univariate and multivariate analyses, receiver operating characteristic curve analysis, and decision curve analysis were performed to determine and compare the predictors of PCa and CSPCa. The results suggested that PI-RADS v2, tPSA, and prostate-specific antigen density （PSAD） were independent predictors of PCa and CSPCa. A PI-RADS v2 score L≥4 provided high negative predictive values （91.39% for PCa and 95.69% for CSPCa）. A model of PI-RADS combined with PSA and PSAD helped to define a high-risk group （PI-RADS score = 5 and PSAD L≥0 15 ng ml-1 cm-3, with tPSA in the gray zone, or PI-RADS score L≥4 with high tPSA level） with a detection rate of 96.1% for PCa and 93.0% for CSPCa while a low-risk group with a detection rate of 6.1% for PCa and 2.2% for CSPCa. It was concluded that the PI-RADS v2 could be used as a reliable and independent predictor of PCa and CSPCa. The combination of PI-RADS v2 score with PSA and PSAD could be helpful in the prediction and diagnosis of PCa and CSPCa and, thus, may help in preventing unnecessary invasive procedures.
基金We would like to thank all the study participants, urologists, and study coordinators for participating in the study. This work was partially funded by the National Key Basic Research Program Grant 973 （2012CB518301）, the Key Project of the National Natural Science Foundation of China （81130047）, National Natural Science Foundation of China （81202001, 81272835）, China Scholarship Council （CSC）, intramural grants from Fudan University and Huashan Hospital, and a research grant from Beckman Coulter, Inc.
文摘The [-2]proPSA （p2PSA） and its derivatives, the p2PSA-to-free PSA ratio （%p2PSA）, and the Prostate Health Index （PHI） have greatly improved discrimination between men with and without prostate cancer （PCa） in prostate biopsies. However, little is known about their performance in cases where a digital rectal examination （DRE） and transrectal ultrasonography （TRUS） are negative. A prospective cohort of 261 consecutive patients in China with negative DRE and TRUS were recruited and underwent prostate biopsies. A serum sample had collected before the biopsy was used to measure various PSA derivatives, including total prostate-specific antigen （tPSA）, free PSA, and p2PSA. For each patient, the free-to-total PSA ratio （%fPSA）, PSA density （PSAD）, p2PSA-to-free PSA ratio （%p2PSA）, and PHI were calculated. Discriminative performance was assessed using the area under the receiver operating characteristic curve （AUC） and the biopsy rate at 91% sensitivity. The AUC scores within the entire cohort with respect to age, tPSA, %fPSA, PSAD, p2PSA, %p2PSA, and PHI were 0.598, 0.751, 0.646, 0.789, 0.814, 0.808, and 0.853, respectively. PHI was the best predictor of prostate biopsy results, especially in patients with a tPSA of 10.1-20 ng ml-1. Compared with other markers, at a sensitivity of 91%, PHI was the most useful for determining which men did not need to undergo biopsy, thereby avoiding unnecessary procedures. The use of PHI could improve the accuracy of PCa detection by predicting prostate biopsy outcomes among men with a negative DRE and TRUS in China.
基金ZHANG Min and ZHANG Nan contributed equally to this work. This work was supported by a grant from the Beijing Natural Science Foundation （No. 7092101）.
文摘Diabetes mellitus （DM） is a considerably common public health problem, which is associated with severecomplications. In China, considerably increasing people are diagnosed as DM each year. It has been reported that DM has an increased risk of several neoplasm, notably cancer of the pancreatic, liver, breast, bladder and colon.1 However,
