Fereshteh Jozaghkar; Abasalt Hosseinzadeh Colagar; Mohammadreza Hosseinzadeh; Faramarz Mehrnejad; Emadoddin Moudi
Abstract
Prostate neoplasms, such as prostate cancer and benign prostatic hyperplasia, are complex and heterogeneous diseases that are caused by environmental, metabolic, and genetic factors. Various reports showed the relationship of several genes, including the HNF1B and LMTK2 genes, in the occurrence of prostate ...
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Prostate neoplasms, such as prostate cancer and benign prostatic hyperplasia, are complex and heterogeneous diseases that are caused by environmental, metabolic, and genetic factors. Various reports showed the relationship of several genes, including the HNF1B and LMTK2 genes, in the occurrence of prostate cancer. This study investigated the association of HNF1B-rs4794758 and LMTK2-rs7791463 polymorphisms with prostate cancer and benign prostatic hyperplasia in a case-control study, followed by bioinformatics analysis. For this purpose, blood samples were collected from 70 healthy men, 58 men with benign prostatic hyperplasia (positive digital rectal examination or DRE and PSA levels below 4 ng/mL), and 70 men with prostate cancer (positive DRE, PSA levels above 4 ng/mL, and diagnoses confirmed by pathological findings). These men were referred to Shahid Beheshti Hospital in Babol. After genomic DNA extraction, the genotype was determined using PCR-RFLP. A genotypic and allelic analysis revealed that the rs4794758 polymorphism with AA genotype (OR: 4.808, 95%CI: 1.260-18.348, P= 0.022) had a significant difference between the prostate cancer group and the benign prostatic hyperplasia group compared to the control group. Allele A of this polymorphism was also significantly associated with prostate cancer (OR: 1.705, 95%CI: 1.055-2.755, P= 0.030). However, there was no correlation between different genotypes of the rs7791463 polymorphism with prostate cancer and benign prostatic hyperplasia. Bioinformatics analysis by some online servers and software showed that the rs4794758 polymorphism possibly changes the hnRNA splicing pattern. So, this polymorphism could probably provide a locus for the TBP transcription factor. In addition, the rs7791463 polymorphism potentially alters the hnRNA splicing pattern and changes the reading frame. Based on the data, HNF1B-rs4794758 polymorphism is associated with prostate cancer susceptibility, which can be considered a molecular risk factor in future studies.
Setare Kakavand; Seyed Abdolhamid Angaji; Behnaz Beikzadeh; Raheleh Roudi; Behzad Narouie
Abstract
Prostate cancer is one of the leading causes of cancer-related deaths among men worldwide. Research has shown that genetic variations can increase an individual's risk of developing this disease. In this study, we investigated the potential role of two genetic variants, one within RFX6 and another within ...
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Prostate cancer is one of the leading causes of cancer-related deaths among men worldwide. Research has shown that genetic variations can increase an individual's risk of developing this disease. In this study, we investigated the potential role of two genetic variants, one within RFX6 and another within SLC22A3, in predisposition to prostate cancer. A genetic association study was conducted, involving a case-control design with 112 prostate cancer cases and 95 individuals affected by benign prostatic hyperplasia who served as controls and had no history of cancer. The genotypes of the two variants, rs339331 in RFX6 and rs9364554 in SLC22A3, were determined using tetra-primer ARMS-PCR. In this study, a multi-stage strategy was employed to analyze the data obtained from genotyping and to assess the association of these two variants with prostate cancer risk. For statistical analysis, Chi-squared, Fisher’s exact test and logistic regression were performed to evaluate the association of variants with prostate cancer and Gleason score. The results suggest that the rs9364554 variant in SLC22A3 is not associated with prostate cancer risk under either additive or multiplicative genetic models, while the variant in RFX6 is significantly associated with prostate cancer susceptibility. The TT genotype of rs339331 indicated a possible protective effect against prostate adenocarcinoma (CI 95% = 0/009 -0/725, P-value = 0/009, OR = 0/083). In conclusion, our study provides evidence that the genetic variant rs339331 within RFX6 is significantly associated with prostate cancer susceptibility and may have a potential protective effect against prostate adenocarcinoma. It should be mentioned that more research is needed to investigate the possible protective effect of the TT genotype of rs9364554 against prostate cancer risk in other populations and various ethnic groups and particularly larger sample sizes are required to confirm this association.
Mina Jahandideh; Ebrahim Barzegari
Abstract
MicroRNAs are interesting as cancer diagnostic and prognostic biomarkers because of their unique tissue expression profiles, higher stability in the blood in comparison to mRNAs, and the possibility for reliable quantification. In the case of prostate cancer (PCa), it is currently ...
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MicroRNAs are interesting as cancer diagnostic and prognostic biomarkers because of their unique tissue expression profiles, higher stability in the blood in comparison to mRNAs, and the possibility for reliable quantification. In the case of prostate cancer (PCa), it is currently emphasized to explore new biomarkers, particularly from microRNAs which are freely available in the bloodstream. In this study, the gene expression omnibus database (GEO), a repository of microarray data for PCa circulating extracellular vesicle-free microRNAs profiling, was analyzed for differentially expressed miRNAs (DE-miRs). Top 20 most differentially expressed miRs with significant (adjusted p-value < 0.01) high expression (fold change) levels were extracted by the simultaneous application of different filtering criteria. Then, microRNA-gene networks were constructed for the two sets of positively (n=20) or negatively (n=20) regulated miRNAs. Gene ontology annotations of the target gene sets were also extracted and analyzed. Results indicated that human miR-1587, miR-223-3p, miR-3125, and miR-642b-3p are highly significant DE-miRs in PCa. In addition, human miR-4459, miR-1273g, miR 642a-3p, and miR-642b-3p were identified as top-ranked hubs in the relevant miRNA-gene networks. FOXK1, PML, CD24, ATN1, BAZ2A, CDKN1A, NUFIP2, and HARNPU were identified as microRNA target genes with significant dysregulation. miR-4459, miR-1273g-3p, miR-3135b, miR-5001-5p, and miR-1587 were proposed as novel microRNAs with the potential to be utilized as diagnostic biomarkers of prostate cancer among circulating vesicle-free miRNAs.
