CircTHSD4 promotes the malignancy and docetaxel (DTX) resistance in prostate cancer by regulating miR-203/HMGA2 axis

Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and docetaxel(DTX)resistance of PCa.Methods:circTHSD4 expression within PCa as well as matched non-carcinoma samples was measured through real time reverse transcription quantitative polymerase chain reaction(RT-qPCR).In addition,a subcellular fraction assay was conducted to determine circTHSD4 subcellular localization within PCa cells.In addition,we performed a Western blot(WB)assay to detect high mobility.group A2 protein(HMGA2)levels.Besides,functional associations of two molecules were investigated through dual luciferase reporter assay.Cell Counting Kit(CCK)-8,colony formation together with Transwell assay was conducted to assess malignant phenotypes of PCa cells,whereas flow cytometry was performed to determine cell apoptosis.Furthermore,a xenograft mouse model was constructed to verify the effect of circTHSD4 on the carcinogenesis of PCa cells.Results:According to RT-qPCR results,circTHSD4 was up-regulated within PCa tissues and cells,which predicted the dismal prognostic outcome of PCa cases.circTHSD4 silencing within PCa cells markedly suppressed cell growth,migration,and colony fomation.circTHSD4 silencing remarkably elevated PCa cell apoptosis and carcinogenesis within the xenograft model.Further,circTHSD4 silencing enhanced docetaxel(DTX)sensitivity in PCa cells.Furthermore,we demonstrated that circTHSD4 modulated the malignancy of PCa cells by regulating HMGA2 expression through sponging miR 203.Conclusion:Together,our findings suggest that cirCTHSD4 overexpression could promote the malignant phenotype and DTX resistance in PCa through the regulation of the miR 203/HMGA2 axis.

LncRNA HCG18 promotes prostate cancer progression by regulating the miR-512-3p/HK-2 axis

ObjectiveLong non-coding RNAs(lncRNAs)play an important role in tumor progression.Numerous studies show that lncRNAs are strongly associated with prostate cancer(PCa)progression.The aim of this study was to investigate the pathway through which lncRNA HCG18 regulates PCa progression by bioinformatics analysis and experiments.MethodsWe compared HCG18 expression in PCa versus normal tissue and cells by data and cell lines,followed by comparing the changes in tumor cell proliferation,migration,and invasive ability after knockdown of HCG18.Then we searched for its downstream pathway by database and validated the pathway in vivo and in vitro.ResultsHCG18 was highly expressed in PCa and has the ability to promote tumor proliferation,migration,and invasion;knockdown of HCG18 led to a decrease in the ability of cells to do so,which can be reversed by knockdown of miR-512-3p or overexpression of hexokinase 2.ConclusionOur in vivo and in vitro experiments suggest that HCG18 can play a role in promoting PCa progression by blocking the inhibition of hexokinase 2 by miR-512-3p via sponge adsorption.

miR-21 targets and inhibits tumor suppressor gene PTEN to promote prostate cancer cell proliferation and invasion:An experimental study

Objective: To study whether miR-21 targets and inhibits tumor suppressor gene PTEN can promote prostate cancer cell proliferation and invasion. Methods: Prostate cancer cell lines PC-3 were cultured and divided into negative control group (NC group), miR-21 group, pcDNA3.1 group, miR-21+pcDNA3.1 group and miR-21+PTEN group that were transfected with different miR and plasmid, respectively. After 12 h and 24 h of transfection, the cell viability and invasive cell number were determined; after 24 h of transfection, Bcl-2, Survivin, MMP2, MMP9, PTEN, PI3K, and AKT expression in cells were determined. Results: After 12 h and 24 h of transfection, OD value and invasive cell number of miR-21 group were significantly higher than those of NC group; after 24 h of transfection, Bcl-2, Survivin, MMP2, MMP9, PI3K and AKT expression levels were significantly higher than those of NC group while PTEN expression level was significantly lower than that of NC group; after 12 h and 24 h of transfection, OD value and invasive cell number of miR-21+pcDNA3.1 group were significantly higher than those of pcDNA3.1 group, and the OD value and invasive cell number of 1niR-21+PTEN group were significantly lower than those of miR-21+pcDNA3.1 group; after 24 h of transfection, Bcl-2, Survivin, MMP2 and MMP9 content of miR-21+pcDNA3.1 group were significantly higher than those of pcDNA3.1 group, and Bcl-2, Survivin, MMP2 and MMP9 content of miR-21+PTEN group were significantly lower than those of miR-21+pcDNA3.1 group. Conclusions: miR-21 can target and inhibit tumor suppressor gene PTEN expression to promote prostate cancer cell proliferation and invasion.

PCA3 and TMPRSS2-ERG gene fusions as diagnostic biomarkers for prostate cancer

The incidence of prostate cancer （PCa） is rising steadily among males in many countries. Serum prostate-specific antigen （PSA） is widely applied to clinical diagnosis and screening of PCa. However, the so-called grey area of PSA levels 4.0-10.0 ng/mL has a low specificity of 25-40% resulting in a high rate of negative biopsy and overtreatment. So in order to treat PCa patients in early stage, there is an urgent need for new biomarkers in PCa diagnosis. The PCA3 gene, a non-coding RNA （ncRNA） that is highly expressed in prostate cancer （PCa） cells, has been identified as a molecular biomarkers to detect PCa, of which PCA3 has already under clinical application. PCA3 is strongly overexpressed in malignant prostate tissue compared to benign or normal adjacent one. Newly, PCA3 is considered to be a promising biomarker in clinical diagnosis and targeted therapy. The diagnostic significance of PCA3, however, is awaiting further researches. Moreover, it has been demonstrated recently that TMPRSS2-ERG gene fusion is identified as the predominant genetic change in patients diagnosed with PCa. Recent study revealed that combination of the PC43 and TMPRSS2-ERG gene fusion test optimizes PCa detection compared with that of single biomarker, which would lead to a considerable reduction of the number of prostate biopsies. In this review, we focused on the potential use of PCA3 and TMPRSS2-ERG gene fusion detection in the diagnosis of PCa.

The role of BRCA 1 and BRCA2 in prostate cancer

One of the strongest risk factors for prostate cancer is a family history of the disease. Germline mutations in the breast cancer predisposition gene 2 （BRCA2） are the genetic events known to date that confer the highest risk of prostate cancer （8.6-fold in men ≤ 65 years）. Although the role of BRCA2 and BRCA1 in prostate tumorigenesis remains unrevealed, deleterious mutations in both genes have been associated with more aggressive disease and poor clinical outcomes. The increasing incidence of prostate cancer worldwide supports the need for new methods to predict outcome and identify patients with potentially lethal forms of the disease. As we present here, BRCA germline mutations, mainly in the BRCA2gene, are one of those predictive factors. We will also discuss the implications of these mutations in the management of prostate cancer and hypothesize on the potential for the development of strategies for sooradic cases with similar characteristics.

The radiation response of androgen-refractory prostate cancer cell line C4-2 derived from androgen-sensitive cell line LNCaP

Radiation therapy is a relatively effective therapeutic method for localized prostate cancer （PCa） patients. However, radioresistance occurs in nearly 30% of patients treated with potentially curative doses. Therapeutic synergy between radiotherapy and androgen ablation treatment provides a promising strategy for improving the clinical outcome. Accordingly, the androgen deprivation-induced signaling pathway may also mediate radiosensitivity in PCa cells. The C4-2 cell line was derived from the androgen-sensitive LNCaP parent line under androgen-depleted condition and had acquired androgen-refractory characteristics. In our study, the response to radiation was evaluated in both LNCaP and C4-2. Results showed that C4-2 cells were more likely to survive from irradiation and appeared more aggressive in their resistance to radiation treatment compared with LNCaP, as measured by clonogenic assays and cell viability and cell cycle analyses. Gene expression analyses revealed that a set of genes involved in cell cycle arrest and DNA repair were differentially regulated in LNCaP and C4-2 in response to radiation, which was also consistent with the radiation-resistant property observed in C4-2 cells. These results strongly suggested that the radiation-resistant property may develop with progression of PCa to androgen- independent status. Not only can the LNCaP and C4-2 PCa progression model be applied for investigating androgen-refractory progression, but it can also be used to explore the development of radiation resistance in PCa.

Human epidermal growth factor receptor type 2 protein expression in Chinese metastatic prostate cancer patients correlates with cancer specific survival and increases after exposure to hormonal therapy

Aim： To investigate human epidermal growth factor receptor type 2 （HER2） protein expression and gene amplification in Chinese metastatic prostate cancer patients and their potential value as prognostic factors. Methods： Immunohistochemistry （IHC） was performed to investigate HER2 protein expression in prostate biopsy specimens from 104 Chinese metastatic prostate cancer patients. After 3-11 months of hormonal therapy, 12 patients underwent transurethral resection of the prostate （TURP）. HER2 protein expression of TURP specimens was compared with that of the original biopsy specimens. Of these, 10 biopsy and 4 TURP specimens with HER2 IHC staining scores ≥ 2＋ were investigated for HER2 gene amplification status by fluorescent in situ hybridization （FISH）. Results： Of the 104 prostate biopsy specimens, HER2 protein expression was 0, 1＋, 2＋ and 3＋ in 49 （47.1%）, 45 （43.3%）, 8 （7.7%） and 2 （1.9%） cases, respectively. There was a significant association between HER2 expression and Gleason score （P = 0.026）. HER2 protein expression of prostate cancer tissues increased in 33.3% of patients after hormonal therapy. None of the 14 specimens with HER2 IHC scores 〉 2＋ showed HER2 gene amplification. Patients with HER2 scores 〉 2＋ had a significantly higher chance of dying from prostate cancer than those with HER2 scores of 0 （P = 0.004） and 1＋ （P = 0.034）. Multivariate Cox regression analysis showed that HER2 protein expression intensity was an independent predictor of cancer-related death （P = 0.039）. Conclusion： An HER2 IHC score 〉 2＋ should be defined as HER2 protein overexpression in prostate cancer. Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer. HER2 protein expression increases in some individual patients after hormonal therapy.

Up-regulation of Bcl-2 is required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage

Bcl-2 is an anti-apoptotic oncoprotein and its protein levels are inversely correlated with prognosis in many cancers. However, the role of Bcl-2 in the progression of prostate cancer is not clear. Here we report that Bcl-2 is required for the progression of LNCaP prostate cancer cells from an androgen-dependent to an androgen-independent growth stage. The mRNA and protein levels of Bcl-2 are significantly increased in androgen-independent prostate cancer cells, shRNA-medi- ated gene silencing of Bcl-2 in androgen-independent prostate cancer cells promotes UV-induced apoptosis and suppresses the growth of prostate tumors in vivo. Growing androgen-dependent cells under androgen-deprivation conditions results in formation of androgen-independent colonies; and the transition from androgen-dependent to androgen-independent growth is blocked by ectopic expression of the Bcl-2 antagonist Bax or Bcl-2 shRNA. Thus, our results demonstrate that Bcl-2 is not only critical for the survival of androgen-independent prostate cancer cells, but is also required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage.

Dual androgen-response elements mediate androgen regulation of MMP-2 expression in prostate cancer cells

Aim： To characterize the matrix metalloproteinases （MMP）-2 promoter and to identify androgen response elements （AREs） involved in androgen-induced MMP-2 expression. Methods： MMP-2 mRNA levels was determined by reverse transcription-polymerase chain reaction （RT-PCR）. MMP-2 promoter-driven luciferase assays were used to determine the fragments responsible for androgen-induced activity. Chromatin-immunoprecipitation assay and electrophoretic mobility shift assays （EMSA） were used to verify the identified AREs in the MMP-2 promoter. Results： Androgen significantly induced MMP-2 expression at the mRNA level, which was blocked by the androgen antagonist bicalutamide. Deletion of a region encompassing base pairs -1591 to -1259 （relative to the start codon） of the MMP-2 promoter led to a significant loss of androgen-induced reporter activity. Additional deletion of the 5＇-region up to -562 bp further reduced the androgen-induced MMP-2 promoter activity. Sequence analysis of these two regions revealed two putative ARE motifs. Introducing mutations in the putative ARE motifs by site-directed mutagenesis approach resulted in a dramatic loss of androgen-induced MMP-2 promoter activity, indicating that the putative ARE motifs are required for androgen-stimulated MMP-2 expression. Most importantly, the androgen receptor （AR） interacted with both motif-containing promoter regions in vivo in a chromatin immunoprecipitation assay after androgen treatment. Furthermore, the AR specifically bound to the wild-type but not mutated ARE motifs-containing probes in an in vitro EMSA assay. Conclusion： Two ARE motifs were identified to be responsible for androgen-induced MMP-2 expression in prostate cancer cells.

The risks, degree of malignancy and clinical progression of prostate cancer associated with the MDM2 T309G polymorphism： a meta-analysis

To determine the risk, malignant degree and clinical progression of prostate cancer （PCa） associated with mouse double-minute 2 protein （MDM2） T309G variants, a meta-analysis was performed on all eligible published studies. Odds ratios （ORs） with 95% confidence intervals （CIs） were estimated to assess these associations in seven studies that included 5151 cases and 1003 controls. In the overall analysis, the 309G allele was significantly associated with a decreased PCa risk （0R=0.85, 95% CI： 0.74-0.97）; this was also the case for the homozygous comparison （0R--0.72, 95% Ch 0.55-0.95） and the dominant genetic model （0R=0.79, 95% Ch 0.65-0.96）. The 309G allele was also found to be significantly associated with lower degrees of PCa malignancy （0R=0.85, 95% Ch 0.75-0.96） in the overall analysis, as well as in the heterozygous comparison （0R=0.79, 95% Ch 0.65-0.96）, homozygous comparison （0R=0.76, 95% Ch 0.58-0.98） and dominant genetic model （0R=0.81, 95% CI： 0.68-0.96）. Furthermore, grouping analysis showed that the 309G allele in Caucasians was significantly correlated with a decreased PCa risk （0R=0.77, 95% Ch 0.61-0.96）; this was also the case in the homozygous comparison （0R=0.51, 95% Ch 0.31-0.86）. The grouping analysis also showed that the 309G variant in Caucasians was significantly associated with a lower degree of PCa malignancy in all of the genetic models. In addition, we found that the 309G variant in Caucasians was significantly associated with a slower PCa clinical progression in all of the genetic models. In summary, our meta-analysis showed that the MDM2 309G variant was significantly associated with a decreased PCa risk, lower malignant degree and slower clinical progression in Caucasians, but there was no obvious association in the Asian population.

Immunohistochemical Analysis of Omi/HtrA2 Expression in Prostate Cancer and Benign Prostatic Hyperplasia

To study the expression and significance of the serine protease Omi/HtrA2 in prostate cancer and benign prostatic hyperplasia. The expression of Omi/HtrA2 was assayed by means of immunohistochemical technique in 41 prostate cancer （Cap）,20 benign prostatic hyperplasia （BPH） and 10 normal prostate （NP） specimens. Omi/HtrA2 expression was positive in 30 （73.17%） prostate cancer specimens, and the positive rate of Omi/HtrA2 was lower in well differentiated than in poorly and moderately differentiated groups （P〈0.05）. By contrast, the cells in normal prostate and benign prostatic hyperplasia groups showed no or weak expression of Omi/HtrA2. Prostate cancer cells in vivo may need Omi/HtrA2 expression for apoptosis, and that Omi/HtrA2 expression might be involved in prostate cancer development.

Prognostic Value of Promoter Hypermethylation of Retinoic Acid Receptor Beta (RARB) and CDKN2 (p16/MTS1) in Prostate Cancer

Objective: The molecular mechanism of prostate cancer is poorly understood. The aim of the study was to investigate the prevalence and prognostic value of promoter hypermethylation of retinoic acid receptor beta (RARB) and p16 among benign prostatic hyperplasia (BPH) and prostate cancer patients. Methods: In this case-control study, 63 patients were included in three groups; 21 with BPH as the control group, 21 with prostate cancer and good prognostic factors (based on prostate-specific antigen, Gleason score and stage) as good prognosis group, and 21 with prostate cancer and poor prognostic features as poor prognosis group. The prostate biopsy specimen of each individual was examined for hypermethylation of RARB and p16 promoters by methylation specific PCR (MSPCR). Results: Seven (33.3%) patients with good prognosis and 15 (71.4%) patients with poor prognosis were positive for RARB methylation, which were significantly higher than controls (P <0.0001). p16 promoter methylation was shown in 19.0% and 47.6% patients with good and poor prognosis, respectively. The RARB and p16 promoter methylation in the poor prognosis group was significantly higher than that in the good prognosis group (P =0.02 for RARB and P<0.0001 for p16). Conclusion: Hypermethylation of RARB and p16 promoters may predict prognosis in prostate cancer.

CircBAGE2(hsa_circ_0061259)regulates CCND1 and PDCD10 expression by functioning as an miR-103a-3p‘sponge’to alter the proliferation and apoptosis of prostate cancer cells

Objective The aim of the article is to explore the function of circBAGE2(hsa_circ_0061259)in prostate cancer(PCa)cells.Methods Sequencing results of circBAGE2 were verified by quantitative RT PCR(qRT-PCR)and Sanger sequencing.Agarose gel electrophoresis was used to detect the resistance of GAPDH,BAGE2,and circBAGE2 to RNase R and their expression as cDNA and gDNAin 22RV1 cells.The biological functions of circBAGE2 were investigated by CCK8 assay and flow cytometry in 22RV1 cells transfected with siRNAs.Multiple databases were used to predict the target binding sites between circRNAs,miRNAs,and mRNAs.Western blotting was used to detect the expression of CCND1 and PDCD10.Results CircBAGE2 was significantly upregulated in PCa samples and PCa cells compared to that in matched normal tissues and normal cells,and CircBAGE2 knockdown inhibits cell proliferation and promotes apoptosis.Downregulation of circBAGE2 compromised the expression of CCND1 and PDCD10.The 3’UTRs of CCND1 and PDCD10 were matched by miR-103a-3p,which shared binding sites with circBAGE2.Conclusion CircBAGE2 contributes to PCa progression by upregulating CCND1 and PDCD10 expression through its role as a‘sponge’of miR-103a-3p.CircBAGE2 may be a potential therapeutic target for PCa.

Mutations in epigenetic regulator KMT2C detected by liquid biopsy are associated with worse survival in prostate cancer patients

Background:KMT2(lysine methyltransferase)family enzymes are epigenetic regulators that activate gene transcription.KMT2C is mainly involved in enhancer-associated H3K4me1,and is also one of the top mutated genes in cancer(6.6%in pan-cancer).Currently,the clinical significance of KMT2C mutations in prostate cancer is understudied.Methods:We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study.We investigated the association between KMT2C mutations,other mutations,and pathways.Furthermore,we evaluated the prognostic value of KMT2C mutations,measured by overall survival(OS)and castration resistance-free survival(CRFS).Also,we explored the prognostic value of KMT2C mutations in different patient subgroups.Lastly,we investigated the predictive value of KMT2C mutations in individuals receiving conventional combined anti-androgen blockade(CAB)and abiraterone(ABI)as measured by PSA progression-free survival(PSA-PFS).Results:The KMT2C mutation rate in this cohort is 7.24%(16/221).KMT2C-mutated patients showed worse survival than KMT2C-wild type(WT)patients regarding both CRFS and OS(CRFS:mutated:9.9 vs.WT:22.0 months,p=0.015;OS:mutated:71.9 vs.WT 137.4 months,p=0.012).KMT2C mutations were also an independent risk factor in OS[hazard ratio:3.815(1.461,9.96),p=0.006]in multivariate analyses.Additionally,we explored the association of KMT2C mutations with other genes.This showed that KMT2C mutations were associated with Serine/Threonine-Protein Kinase 11(STK11,p=0.004)and Catenin Beta 1(CTNNB1,p=0.008)mutations.In the CAB treatment,KMT2C-mutated patients had a significantly shorter PSA-PFS compared to KMT2C-WT patients.(PSA-PFS:mutated:9.9 vs.WT:17.6 months,p=0.014).Moreover,KMT2C mutations could effectively predict shorter PSA-PFS in 10 out of 23 subgroups and exhibited a strong trend in the remaining subgroups.Conclusions:KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CRFS and OS,and KMT2C mutations were associated with STK11 and CTNNB1 mutations.Furthermore,KMT2C mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer.

Prostate cancer antigen-1 as a cancer potential novel marker for prostate

Aim： To examine the expression of prostate cancer antigen-1 （PCA-1） in prostate cancer （PCa） and to validate it as a potential marker for diagnosis of PCa. Methods： In situ hybridization analysis of PCA-1 mRNA expression was performed on 40 benign prostate hyperplasia （BPH）, 16 high-grade prostatic intraepithelial neoplasm （HG-PIN）, 74 PCa and 34 other malignant carcinoma specimens. The level of PCA- 1 expression was semiquanfitatively scored by assessing both the percentage and intensity of PCA- 1 positive staining cells in the specimens. We then compared the PCA-1 expression between BPH, HG-PIN and PCa and evaluated the correlation of PCA-1 expression level with clinical parameters of PCa. Results： PCA-1 mRNA was expressed in the majority of both PCa and HG-PIN specimens but not in BPH and other malignant carcinoma. The expression level of PCA-1 increased along with a high Gleason score （P 〈 0.05）, and was unrelated to other clinical parameters of PCa （all P 〉 0.05）. Conclusion： The data suggest that PCA-1 might be a novel diagnostic marker for PCa, and that increased PCA-1 expression might denote more aggressive variants of PCa.

Immunohistochemical Studies of the Expression of Matrix Metalloproteinase-2 and Metalloproteinase-9 in Human Prostate Cancer

To study the expression of matrix metalloproteinase 2 and 9 in human prostate cancer, matrix metalloproteinase 2 and 9 were immunohistochemically detected in tissues of prostate cancer and benign prostatic hyperplasia (BPH). Our results showed that matrix metalloproteinase 2 and 9 levels in prostate cancer were much higher than those in tissues of BPH, with the cancer invasion being positively correlated with the expression of the metalloproteinases. It is concluded that matrix metalloproteinase 2 and 9 are better molecular markers, which are of help in the diagnosis and prediction of prognosis of prostate cancer.

Identification and Localization of Prostate Cancer with Combined Use of T2-Weighted,Diffusion Weighted MRI and Proton MR Spectroscopy,Correlation with Histopathology

Purpose: To predict the diagnostic performance of combined use of T2-weighted imaging (T2W)-diffusion weighted MRI (DWI) and apparent diffusion coefficient (ADC)-proton MR spectroscopy (H-MRS) for the detection of prostate cancer, correlated to histopathology as the reference standard. Method: After institutional review board approval, 40 patients with prostate cancer were included in this retrospective research. Two readers evaluated the results of T2W, DWI-ADC mapping and H-MRS independently for the depiction of prostate cancer. Reference standard was the TRUS-guided biopsy and the surgical histopathological results. Statistical analysis was assessed by Fisher’s exact t-test, Wilcoxon signed rank test, variance analysis test with Kappa (k) values and receiver operating characteristics (ROC) curve for ADC values, Cho/Cit and Cho + Cre/Cit ratios for each observer. Results: Both readers declined 46% sensitivity and 68% specificity for T2W sequence, 29% sensitivity and 82% specificity for DWI-ADC mapping and 49% specificity for Cho/Cit and Cho + Cre/Cit ratios, 69% sensitivity for Cho/Cit 70% sensitivity for Cho + Cre/Cit ratios of H-MRS. T2W + DWI-ADC mapping + H-MRS (Cho/Cit and Cho + Cre/Cit ratios) regarded 81% sensitivity and 66% specificity, with significant statistical differences to the reference histopathology (p 0.05). Conclusion: Combination of T2W, DWI and H-MRS were more sensitive and more accurate than either sequences alone, for prostate cancer localization and detection.

Human Kallikrein-2 and Free Prostate Specific Antigen as Biomarkers for Early Detection of Prostate Cancer, Sudan: A Case-Control Study

Background: Prostate cancer (PCa) is considered one of the major health threats facing males in Sudan. Prostate-specific antigen (PSA) test is the most important laboratory test used in the diagnosis of prostate cancer, the main disadvantage of PSA is its limited specificity, which triggered a lot of interest in development, more research on other markers such as serum human kallikrein-2 (KLK-2) and free prostate specific antigen (fPSA). Objectives: To evaluate the validity of serum kallikrein-2 (KLK-2) and free prostate specific antigen (fPSA) in the early detection of prostate cancer among Sudanese patients. Method: In this study seventy men were considered as a case subject, who were diagnosed as cancer prostate at Gezira Hospital for Renal Disease and Surgery (GHRDS), Sudan during the period February 2018 to July 2019. Randomly selected sixty patients of BPH patients and forty-five apparently healthy men as control subject. KLK-2, fPSA and PSA estimations were performed from serum samples using the principle of Enzyme Linked Immunosorbent Assay (ELISA). Results: The results revealed a highly significant difference between the serum levels individual biomarkers (KLK-2, fPSA, PSA) and multiple biomarkers (fPSA/PSA, KLK-2/fPSA, KLK-2/PSA) for patients with prostate cancer when compared with the control groups. Furthermore, the fPSA/PSA ratio was lower in the patients with prostate cancer (P value = 0.00) than in the control group, the fPSA/PSA ratio showed that best accuracy to differentiate prostate cancer from control group, fPSA cut-off value was found to be more than (18 ng/ml), with sensitivity (93%), specificity (80%), and odds ratio (55). Conclusions: The use of multiple biomarkers rather than individual biomarkers especially fPSA/PSA ratio improves the specificity as well as maintenance of higher sensitivity for early diagnosis of the prostate cancer.

Detection of TMPRSS2：ERG fusion gene in circulating prostate cancer cells

Aim： To investigate the existence of TMPRSS2：ERG fusion gene in circulating tumor cells （CTC） from prostate cancer patients and its potential in monitoring tumor metastasis. Methods- We analyzed the frequency of TMPRSS2： ERG and TMPRSS2：ETV1 transcripts in 27 prostate cancer biopsies from prostatectomies, and TMPRSS2：ERG transcripts in CTC isolated from 15 patients with advanced androgen independent disease using reverse transcription polymerase chain reaction （RT-PCR）. Fluorescence in situ hybridization （FISH） was applied to analyze the genomic truncation of ERG, which is the result of TMPRSS2：ERG fusion in 10 of the 15 CTC samples. Results： TMPRSS2： ERG transcripts were found in 44% of our samples, but we did not detect expression of TMPRSS2：ETV1. Using FISH analysis we detected chromosomal rearrangements affecting the ERG gene in 6 of 10 CTC samples, including 1 case with associated TMPRSS2：ERG fusion at the primary site. However, TMPRSS2：ERG transcripts were not detected in any of the 15 CTC samples, including the 10 cases analyzed by FISH. Conclusion： Although further study is required to address the association between TMPRSS2：ERG fusion and prostate cancer metastasis, detection of genomic truncation of the ERG gene by FISH analysis could be useful for monitoring the appearance of CTC and the potential for prostate cancer metastasis.

UGT2B17 status and risk of prostate cancer: A meta-analysis

Objective: Recent studies on the association between Uridine diphosphoglucuronosyl tranferases (UGT) 2B17 status and risk of prostate cancer (PCa) showed inconclusive results. To clarify this possible association, we conducted a meta-analysis of published studies. Methods: We searched published literature from PubMed, Embase, Google Scholar and China National Knowledge Infrastructure (CNKI). According to our inclusion criteria, studies that observed the association between UGT2B17 status and PCa risk were included. The principal outcome measure was the adjusted odds ratio (OR) with 95% confidence interval (CI) for the risk of PCa associated with UGT2B17 status. Results: A total of 6 studies with 7029 subjects (3839 cases and 3190 controls) were eligible for inclusion in the meta-analysis. Overall, there was a significant association between UGT2B17 status and increased risk of prostate cancer (OR = 1.74, 95% CI 1.14 - 2.64, P 0.001). Similar results were found in the subgroup analyses by ethnicity and types of controls. Conclusion: This meta-analysis demonstrates that UGT2B17 status is associated with prostate cancer susceptibility, and it contributes to increased risk of prostate cancer.