Occurrence Of Prostate Cancer Research Articles

Development and validation of an imageless machine-learning algorithm for the initial screening of prostate cancer.

Prostate specific antigen (PSA) testing is a low-cost screening method for prostate cancer (PCa). However, its accuracy is limited. While progress is being made using medical imaging for PCa screening, PSA testing can still be improved as an easily accessible first step in the screening process. We aimed to develop and validate a new model by further personalizing the analysis of PSA with demographic, medical history, lifestyle parameters, and digital rectal examination (DRE) results. Using data from 34,224 patients in the screening arm of the PLCO trial (22,188 for the training set and 12,036 for the validation set), we applied a gradient-boosting model whose features (Model 1) were one PSA value and the personal variables available in the PLCO trial except those that signaled an ex-anteassumption of PCa. A second algorithm (Model 2) included a DRE result. The primary outcome was the occurrence of PCa, while the aggressiveness of PCa was a secondary outcome. ROC analyses were used to compare both models to other initial screening tests. The areas under the curve(AUC) for Model 2 was 0.894 overall and 0.908 for patients with a suspicious DRE, compared to 0.808 for PSA for patients with a suspicious DRE. The AUC for Model 1 was 0.814 compared to 0.821 for PSA. Model 2 predicted 58% more high-risk PCa than PSA ≥4 combined with an abnormal DRE and had a positive predictive value of 74.7% (vs. 50.6%). Personalizing the interpretation of PSA values and DRE results with a gradient-boosting model showed promising results as a potential novel, low-cost method for the initial screening of PCa. The importance of DRE, when included in such a model, was also highlighted.

CD44 and CD133 protein expression might serve as a prognostic factor for early occurrence castration-resistant prostate cancer.

The occurrence of castration-resistant prostate cancer (CRPC) varies in patients with advanced prostate cancer (PCa) undergoing androgen deprivation therapy (ADT). The rate of occurrence of CRPC may be related to the presence of prostate cancer stem cells (CSC). Thus, this study aims to evaluate the presence of CSC markers (CD44 and CD133) in histopathology tissue at the time of diagnosis and their correlation with the occurrence of CRPC in patients with advanced PCa within 2 years of ADT. A retrospective case-control study was conducted to evaluate the incidence of CRPC within 2 years. The inclusion criteria were patients with PCa who had received treatment with ADT and a first-generation anti-androgen (AA) for 2 years. We classified patients based on whether they developed CRPC within 2 years (CRPC) of the therapy or did not experience CRPC within 2 years (non-CRPC) of the therapy. We performed immunohistochemical (IHC) staining for CD44 and CD133 on the prostate biopsy tissue samples. Data were collected from records spanning 2011-2019. We analyzed a total of 65 samples, including 22 patients with CRPC and 43 patients with non-CRPC who had received treatment with LHRH agonists and AA for up to 2 years. Our findings showed a significant H-score difference in CD44 protein expression between CRPC prostate adenocarcinoma samples 869 (200-1329) and non-CRPC 524 (154-1166) (p = 0.033). There was no significant difference in CD133 protein expression between the two groups (p = 0.554). However, there was a significant difference in the nonoccurrence of CRPC between the high expressions of both CD44 and CD133 groups with other expressions of CD44/CD133 groups (25% vs. 75%; p = 0.011; odds ratio = 4.29; 95% confidence interval [1.34, 13.76]). This study found a low expression of at least one CD44/CD133 protein in the patients without early occurrence of CRPC. This result might suggest that CD44/CD133 may function as a potential prognostic marker for PCa, especially in a low expression, to identify patients who have a better prognosis regarding the occurrence of early CRPC.

Exploring the Relationship Between Hepatitis C Virus Infection and Prostate Cancer Risk: A National Health and Nutrition Examination Survey Analysis.

Introduction Prostate cancer and hepatitis C virus (HCV) infection stand as notable worldwide health issues. Investigating the connection between HCV infection and the risk of prostate cancer remains an ongoing endeavor, complicated by contradictory findings in prior research. It is imperative to comprehend this potential relationship in order to enhance strategies for prevention and treatment. This paper seeks to delve into the association between HCV infection and prostate cancer by analyzing data from the National Health and Nutrition Examination Survey (NHANES), a comprehensive cross-section of the US population. Methods Information extracted from the NHANES dataset encompassed the period spanning from March 2017 to March 2020, with a focus on the "medical conditions" and "hepatitis" segments. Employing logistic regression analysis, we aimed to discern the connection between HCV infection and the prior occurrence of prostate cancer. This analysis was conducted while factoring in variables such as weight, hypertension, hyperlipidemia, race, educational level, and marital status to ensure the accuracy of the findings. The results of this examination yielded adjusted odds ratios (OR), coefficients of association (B), and corresponding confidence intervals (CI). Results The outcomes derived from the comprehensive multivariate logistic regression analysis, utilizing NHANES data, indicated an absence of a statistically noteworthy correlation between HCV infection and the probability of prostate cancer occurrence. While accounting for diverse variables like weight, hypertension, hyperlipidemia, race, educational level, and marital status, no substantial relationship was observed between HCV infection and the risk of prostate cancer. These results are consistent with earlier investigations that similarly struggled to establish a definitive connection between HCV infection and the incidence of prostate cancer. Conclusion Drawing from NHANES data, this study indicates the absence of a substantial link between HCV infection and the incidence of prostate cancer. The divergent findings observed in prior research accentuate the intricate nature of the connection between HCV infection and prostate cancer. Future investigations should encompass more extensive sample sizes, prospective frameworks, and a meticulous assessment of potential variables that might confound the results. Furthermore, it is important to examine the potential protective impact of HCV infection due to antiviral interventions and its effect on the associated risk of prostate cancer. Such endeavors would offer valuable insights for individuals grappling with these health challenges.

Novel estrogen receptor β/histone deacetylase dual-targeted near-infrared fluorescent probes as theranostic agents for imaging and treatment of prostate cancer

Estrogen receptor (ER) β and histone deacetylases (HDACs), when overexpressed, are associated closely with the occurrence and development of prostate cancer and are, therefore, considered important targets and biomarkers used in the clinical treatment of prostate cancer. The present study involved the design and synthesis of the first ERβ and HDAC dual-target near-infrared fluorescent probe with both imaging capacity and antitumor activity for prostate cancer. Both P1 and P2 probes exhibited excellent ERβ selectivity, with P1 being almost exclusively selective for ERβ compared to ERα. In addition, P1 exhibited good optical properties, such as strong near-infrared emission, large Stokes shift, and better anti-interference ability, along with excellent imaging ability for living cells. P1 also exhibited potent inhibitory activity against HDAC6 and DU-145 cells, with IC50 values of 52 nM and 0.96 μM, respectively. Further, P1 was applied successfully for the in vivo imaging of prostate cancer in a mouse model, and significant in vivo antitumor efficacy was achieved. The developed dual-target NIR fluorescent probe is expected to serve as an effective tool in the research on prostate cancer, leading to novel insights for the theranostic study of diseases related to ERβ and HDACs.

TUMOR MICROENVIRONMENT-ASSOCIATED miR-7-5p, miR-19a-3p, AND miR-23b-3p EXPRESSION IN PROSTATE CANCER WITH DIFFERENT PROGRESSION RISK.

The tumor microenvironment (TME) plays an important role in the occurrence and progression of prostate cancer (PCa). At the same time, the mechanisms and features of the interaction between tumor cells and individual components of the TME in PCa remain not fully elucidated. The aim was to study the expression levels of tumor-associated miR-7-5p, miR-19a-3p, and miR-23b-3p in the PCa tissue and to analyze their relationship with the features of TME. The work is based on the analysis of the results of the examination and treatment of 50 patients with PCa of stages II-IV. The expression of miRNA in the PCa tissue was analyzed by the real-time polymerase chain reaction. The expression of alpha-smooth muscle actin (α-SMA), vimentin (VIM), and CD68 in PCa tissue was determined by the immunohistochemical method. The identification of mast cells in the PCa tissue was assessed by the histochemical method. The analysis of the expression levels of tumor-associated miRNAs demonstrated that the tumor tissue of patients with a high risk of PCa progression was characterized by 4.93 (p < 0.01) and 8.97 (p < 0.05) times higher levels of miR-19a-3p and miR-23b-3p, respectively, compared to similar indicators in the group of patients with a low risk of PCa progression. The levels of miR-7-5p and miR-19a-3p expression in the PCa tissue correlated with the expression level of α-SMA (r = 0.49 and r = 0.45, respectively; p < 0.05) and VIM (r = 0.45 and r = 0.46; respectively, p < 0.05). A direct relationship (r = 0.44; p < 0.05) was established between the level of miR-7-5p expression and the degree of infiltration of the prostate gland tissue by tumor-associated macrophages. The features of the expression of tumor-associated miR-7-5p, miR-19a-3p, and miR-23b-3p indicated the prospect of their use as markers of the aggressiveness of the PCa course.

Harnessing tumor-derived exosomes: A promising approach for the expansion of clinical diagnosis, prognosis, and therapeutic outcome of prostate cancer.

Prostate cancer is the second leading cause of men's death worldwide. Although early diagnosis and therapy for localized prostate cancer have improved, the majority of men with metastatic disease die from prostate cancer annually. Therefore, identification of the cellular-molecular mechanisms underlying the progression of prostate cancer is essential for overcoming controlled proliferation, invasion, and metastasis. Exosomes are small extracellular vesicles that mediate most cells' interactions and contain membrane proteins, cytosolic and nuclear proteins, extracellular matrix proteins, lipids, metabolites, and nucleic acids. Exosomes play an essential role in paracrine pathways, potentially influencing Prostate cancer progression through a wide variety of mechanisms. In the present review, we outline and discuss recent progress in our understanding of the role of exosomes in the Prostate cancer microenvironment, like their involvement in prostate cancer occurrence, progression, angiogenesis, epithelial-mesenchymal transition, metastasis, and drug resistance. We also present the latest findings regarding the function of exosomes as biomarkers, direct therapeutic targets in prostate cancer, and the challenges and advantages associated with using exosomes as natural carriers and in exosome-based immunotherapy. These findings are a promising avenue for the expansion of potential clinical approaches.

Metabolic analysis using HR-MAS in prostate tissue for prostate cancer diagnosis.

In this study we used nuclear magnetic resonance spectroscopy in prostate tissue to provide new data on potential biomarkers of prostate cancer in patients eligible for prostate biopsy. Core needle prostate tissue samples were obtained. After acquiring all the spectra using a Bruker Avance III DRX 600 spectrometer, tissue samples were subjected to routine histology to confirm presence or absence of prostate cancer. Univariate and multivariate analyses with metabolic and clinical variables were performed to predict the occurrence of prostate cancer. A total of 201 patients, were included in the study. Of all cores subjected to high-resolution magic angle spinning (HR-MAS) followed by standard histological study, 56 (27.8%) tested positive for carcinoma. According to HR-MAS probe analysis, metabolic pathways such as glycolysis, the Krebs cycle, and the metabolism of different amino acids were associated with presence of prostate cancer. Metabolites detected in tissue such as citrate or glycerol-3-phosphocholine, together with prostate volume and suspicious rectal examination, formed a predictive model for prostate cancer in tissue with an area under the curve of 0.87, a specificity of 94%, a positive predictive value of 80% and a negative predictive value of 84%. Metabolomics using HR-MAS analysis can uncover a specific metabolic fingerprint of prostate cancer in prostate tissue, using a tissue core obtained by transrectal biopsy. This specific fingerprint is based on levels of citrate, glycerol-3-phosphocholine, glycine, carnitine, and 0-phosphocholine. Several clinical variables, such as suspicious digital rectal examination and prostate volume, combined with these metabolites, form a predictive model to diagnose prostate cancer that has shown encouraging results.

Extracellular vesicles related gene HSPH1 exerts anti-tumor effects in prostate cancer via promoting the stress response of CD8 + T cells.

T cell stress response state (TSTR), as a novel immune concept previous studies have proposed, has not yet been explored in prostate cancer (PC). As a type of cellular efflux, exosomes play important roles in the occurrence and development of PC. Here, we conducted a combined analysis on extracellular vesicle related genes (EVRGs) in PC using data from single-cell RNA (scRNA), spatial transcriptome (ST), and bulk RNA sequencing. Preliminary findings have revealed that heat shock protein family H (Hsp110) member 1 (HSPH1) possesses two identities, one being EVRGs and the other being a member of the heat shock protein family involved in TSTR, which may promote the differentiation of conventional T cells towards Th1 or Th2 cells through the pathway of IL2-MYC-IL2RA, thereby promoting the increase of CD8 + T cells in the tumor area, especially in the invasive zone, and inhibiting the invasion of PCs. We also notice the negative response of HSPH1 + CD8 + T cell related genes in immune checkpoint blockade (ICB). Western blot (WB) and droplet digital Polymerase Chain Reaction (ddPCR) demonstrated that the mRNA and protein levels of HSPH1 in EVs of PCs were significantly higher than those in adjacent tissues. Results above indicate the potential of HSPH1 as a critical therapeutic target in PC.

The Potential of Extracellular Matrix- and Integrin Adhesion Complex-Related Molecules for Prostate Cancer Biomarker Discovery.

Prostate cancer is among the top five cancer types according to incidence and mortality. One of the main obstacles in prostate cancer management is the inability to foresee its course, which ranges from slow growth throughout years that requires minimum or no intervention to highly aggressive disease that spreads quickly and resists treatment. Therefore, it is not surprising that numerous studies have attempted to find biomarkers of prostate cancer occurrence, risk stratification, therapy response, and patient outcome. However, only a few prostate cancer biomarkers are used in clinics, which shows how difficult it is to find a novel biomarker. Cell adhesion to the extracellular matrix (ECM) through integrins is among the essential processes that govern its fate. Upon activation and ligation, integrins form multi-protein intracellular structures called integrin adhesion complexes (IACs). In this review article, the focus is put on the biomarker potential of the ECM- and IAC-related molecules stemming from both body fluids and prostate cancer tissue. The processes that they are involved in, such as tumor stiffening, bone turnover, and communication via exosomes, and their biomarker potential are also reviewed.

Functional pri-miR-34b/c rs4938723 and KRAS 3′UTR rs61764370 SNPs: Novel phenotype modifiers in Li-Fraumeni Syndrome?

PurposeLi-Fraumeni Syndrome (LFS) is a rare cancer predisposing condition caused by germline pathogenic TP53 variants, in which core tumors comprise sarcomas, breast, brain and adrenocortical neoplasms. Clinical manifestations are highly variable in carriers of the Brazilian germline founder variant TP53 p.R337H, possibly due to the influence of modifier genes such as miRNA genes involved in the regulation of the p53 pathway. Herein, we investigated the potential phenotypic effects of two miRNA-related functional SNPs, pri-miR-34b/c rs4938723 and 3′UTR KRAS rs61764370, in a cohort of 273 LFS patients from Southern and Southeastern Brazil. MethodsThe genotyping of selected SNPs was performed by TaqMan® allelic discrimination and subsequently custom TaqMan® genotyping results were confirmed by Sanger sequencing in all SNP-positive LFS patients. ResultsAlthough the KRAS SNP showed no effect as a phenotype modulator, the rs4938723 CC genotype was significantly associated with development of LFS non-core tumors (first tumor diagnosis) in p.R337H carriers (p = 0.039). Non-core tumors were also more frequently diagnosed in carriers of germline TP53 DNA binding domain variants harboring the rs4938723 C variant allele. Previous studies described pri-miR-34b/c rs4938723 C as a risk allele for sporadic occurrence of thyroid and prostate cancers (non-core tumors of the LFS spectrum). ConclusionWith this study, we presented additional evidence about the importance of analyzing miRNA genes that could indirectly regulate p53 expression, and, therefore, may modulate the LFS phenotype, such as those of the miR-34 family.

Abstract B055: Association between dietary patterns and occurrence of prostate cancer among Nigerian men: The CaPTC Familial Cohort Study

Abstract Background: Prostate cancer (PCa) in men is, to date, the number one cause of death from cancer worldwide. PCa has been associated with a large number of lifestyle factors, including unhealthy dietary habits. In particular, diet and nutrition have been shown to play pivotal roles in PCa, and the habitual consumption of certain specific foods like meat cooked at very high temperatures has been implicated. However, this has not been documented among Black men. The aim of this study was to determine the association between dietary patterns and their association with the occurrence of prostate cancer. Method: This is a longitudinal multisite Prostate Cancer Transatlantic Consortium (CaPTC) familial cohort phase 2 study. Participants were Nigerian Black men between 35 and 70 years old who were willing to participate in the study over a 10-year period. For the food variety score, a score of 1 was given for each food item eaten weekly, and the aggregate food variety score was totaled and categorized as ≥54% very good, 45%–53% was good, 36%–44% fair, 18%–35% poor and &amp;lt;18% was very poor. Data were analyzed using descriptive statistics, such as frequency analyses. Chi-square analysis was used to evaluate dichotomous variables to compare groups based on demographic factors and the occurrence of PCa. Multivariate logistic regression was used to determine the specific predictors of the diagnosis of PCa with potential adjustment for the other demographic variables. P-values &amp;lt; 0.05 was set as significant. Results: A total of 780 participants were recruited, with 72.6% reporting no history of cancer. The median age was 47.00 (range: 21-97),16.5% have been diagnosed with Pca, and 1.5% were diagnosed with other Cancers. Age of cancer diagnosis showed that 21% were diagnosed at about 50 years. Participants’ fruit consumption showed that 28.4%, 29%, 39.5%, 23%, 31%, 28.7%, and 39.2, ate apples, mango, citrus, papaya, green banana, tomatoes, and watermelon, weekly, respectively. Fish was the most consumed protein source of animal origin irrespective of the cooking methods categories, such as boiling, frying, grilling, and smoking. The median food variety score was 20 (0-67), with 8.5%, 3.8%,49.3%, and 26.8% classified as good, very good, poor, and very poor, respectively. Multivariate analysis showed that the category of food variety score (P=0.0009), age (P&amp;lt;0.0001), and grilled fish consumption (P=0.0333) were found to be associated with Pca occurrence. Conclusions: The study showed that food variety score, age, and fish consumption were the correlates of prostate cancer occurrence in the population studied. Citation Format: Opeyemi O. Bolajoko, Catherine A. Oladoyinbo, Daniel Lee, Oluwaseyi Toye, Parisa Fathi, Robert Turesky, Ademola Popoola, Iya Bassey, Solomon Rotimi, Paul Jibrin, Chidebere Ogo, Abidemi Omonisi, Adebanji Adeniji, Anthonia Showunmi, Omolara Fatiregun, Ayo Salako, Haruna Nggada, Faruk Mohammed, Ifeoma Okoye, Ernie Kaninjing, Folakemi Odedina. Association between dietary patterns and occurrence of prostate cancer among Nigerian men: The CaPTC Familial Cohort Study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B055.

Novel Gene Signatures for Prostate Cancer Detection: Network Centralitybased Screening with Experimental Validation

Background: Prostate cancer (PCa) is a kind of malignant tumor with high incidence among males worldwide. The identification of novel biomarker signatures is, therefore of clinical significance for PCa precision medicine. It has been acknowledged that the breaking of stability and vulnerability in biological network provides important clues for cancer biomarker discovery. Methods: In this study, a bioinformatics model by characterizing the centrality of nodes in PCa-specific protein-protein interaction (PPI) network was proposed and applied to identify novel gene signatures for PCa detection. Compared with traditional methods, this model integrated degree, closeness and betweenness centrality as the criterion for Hub gene prioritization. The identified biomarkers were validated based on receiver-operating characteristic evaluation, qRT-PCR experimental analysis and literature-guided functional survey. Results: Four genes, i.e., MYOF, RBFOX3, OCLN, and CDKN1C, were screened with average AUC ranging from 0.79 to 0.87 in the predicted and validated datasets for PCa diagnosis. Among them, MYOF, RBFOX3, and CDKN1C were observed to be down-regulated whereas OCLN was over-expressed in PCa groups. The in vitro qRT-PCR experiment using cell line samples convinced the potential of identified genes as novel biomarkers for PCa detection. Biological process and pathway enrichment analysis suggested the underlying role of identified biomarkers in mediating PCa-related genes and pathways including TGF-β, Hippo, MAPK signaling during PCa occurrence and progression. Conclusion: Novel gene signatures were screened as candidate biomarkers for PCa detection based on topological characterization of PCa-specific PPI network. More clinical validation using human samples will be performed in future work.

Caspase-Linked Programmed Cell Death in Prostate Cancer: From Apoptosis, Necroptosis, and Pyroptosis to PANoptosis.

Prostate cancer (PCa) is a complex disease and the cause of one of the highest cancer-related mortalities in men worldwide. Annually, more than 1.2 million new cases are diagnosed globally, accounting for 7% of newly diagnosed cancers in men. Programmed cell death (PCD) plays an essential role in removing infected, functionally dispensable, or potentially neoplastic cells. Apoptosis is the canonical form of PCD with no inflammatory responses elicited, and the close relationship between apoptosis and PCa has been well studied. Necroptosis and pyroptosis are two lytic forms of PCD that result in the release of intracellular contents, which induce inflammatory responses. An increasing number of studies have confirmed that necroptosis and pyroptosis are also closely related to the occurrence and progression of PCa. Recently, a novel form of PCD named PANoptosis, which is a combination of apoptosis, necroptosis, and pyroptosis, revealed the attached connection among them and may be a promising target for PCa. Apoptosis, necroptosis, pyroptosis, and PANoptosis are good examples to better understand the mechanism underlying PCD in PCa. This review aims to summarize the emerging roles and therapeutic potential of apoptosis, necroptosis, pyroptosis, and PANoptosis in PCa.

Interleukins-6 −174G/C (rs1800795) and −572C/G (rs1800796) polymorphisms and prostate cancer risk

Prostate cancer (PCa) is an aggressive cancer influenced by a complex interplay of genetic and environmental factors. Amongst these risk factors, the impact of Interleukin6 (IL6) gene polymorphisms in PCa risk has received a lot of attention. IL-6 is a cytokine that has been implicated in the pathogenesis of several malignancies, including PCa. Two IL-6 gene polymorphisms, − 174 G/C (rs1800795) and − 572 C/G (rs1800796), have received intellectual attention due to their potential role as modulators of prostate cancer risk. The main objective of this research was to comprehensively explore the potential associations between IL-6 rs1800795 and rs1800796 polymorphisms, and their impact on the occurrence of PCa. A case-control study was carried out with a well-defined cohort comprising 110 PCa cases and 110 controls (total n = 220). The genotyping of rs1800795 and rs1800796 was carefully performed using the highly sensitive and accurate Polymerase Chain Reaction-High Resolution Melting Curve (PCR-HRM) technique. The assessment of genetic associations was evaluated using various R packages, such as Haplo-Stats, SNP stat, pheatmap, and LD heatmap. The present study applied odds ratio (OR) analysis to reveal significant evidence of strong associations between the genotypes of rs1800795 and rs1800796 and the susceptibility to PCa. The findings of this study underscore the noteworthy impact of genetic variations in the IL-6 gene on the development of prostate cancer. Specifically, the C/G and G/G genotypes of rs1800795 demonstrated increased PCa risk, with odds ratios (OR) of 1.650 (95% CI = 1.068–2.549, p = 0.032) and 2.475 (95% CI = 1.215–5.043, p < 0.001), respectively. Similarly, the G/C genotype of rs1800796 exhibited an OR of 2.374 (95% CI = 1.363–4.130, p = 0.012) for elevated prostate cancer risk, while the C/C genotype had an OR of 1.81 (95% CI = 1.02–3.22, p = 0.7). Furthermore, our haplotype analysis have revealed an association between haplotype 4 (C-G) and increased risk of PCa (OR = 1.69, 95% CI = 1.05–2.73, p = 0.032). In conclusion, this case-control analysis presents compelling evidence for a significant association between IL-6 variants (rs1800795 and rs1800796) and increased susceptibility to prostate cancer.

Molecular pathogenesis, mechanism and therapy of Cav1 in prostate cancer.

Prostate cancer is the second incidence of malignant tumors in men worldwide. Its incidence and mortality are increasing year by year. Enhanced expression of Cav1 in prostate cancer has been linked to both proliferation and metastasis of cancer cells, influencing disease progression. Dysregulation of the Cav1 gene shows a notable association with prostate cancer. Nevertheless, there is no systematicreview to report about molecular signal mechanism of Cav1 and drug treatment in prostate cancer. This article reviews the structure, physiological and pathological functions of Cav1, the pathogenic signaling pathways involved in prostate cancer, and the current drug treatment of prostate cancer. Cav1 mainly affects the occurrence of prostate cancer through AKT/mTOR, H-RAS/PLCε, CD147/MMPs and other pathways, as well as substance metabolism including lipid metabolism and aerobic glycolysis. Baicalein, simvastatin, triptolide and other drugs can effectively inhibit the growth of prostate cancer. As a biomarker of prostate cancer, Cav1 may provide a potential therapeutic target for the treatment of prostate cancer.

Prostate Cancer in Transplant Receivers-A Narrative Review on Oncological Outcomes.

Prostate cancer (PCa) is a low tumor mutational burden (TMB) cancer with a poor response to immunotherapy. Nonetheless, immunotherapy can be useful, especially in metastatic castration-resistant PCa (mCRPC). Increased cytotoxic T lymphocytes (CTLs) density is correlated with a shorter overall survival (OS), an early biochemical relapse, and a generally poor PCa prognosis. An increased number of CCR4+ regulatory T cells (CCR4 + Tregs) relates to a higher Gleason score or earlier progression. The same therapeutic options are available for renal transplant recipients (RTRs) as for the population, with a comparable functional and oncological outcome. Radical retropubic prostatectomy (RRP) is the most common method of radical treatment in RTRs. Brachytherapy and robot-assisted radical prostatectomy (RARP) seem to be promising therapies. Further studies are needed to assess the need for prostatectomy in low-risk patients before transplantation. The rate of adverse pathological features in RTRs does not seem to differ from those observed in the non-transplant population and the achieved cancer control seems comparable. The association between PCa and transplantation is not entirely clear. Some researchers indicate a possible association between a more frequent occurrence of PCa and a worse prognosis in advanced or metastatic PCa. However, others claim that the risk and survival prognosis is comparable to the non-transplant population.

Sexually and Non-sexually Transmitted Infections and The risk of Prostate Cancer

Abstract Introduction Prostate cancer (PCa) is by far the most common type of cancer among men in western countries. However, relatively little is known about its etiology despite the high morbidity and mortality rates, where only advanced age, ethnicity, and family history of prostate cancer are well-established non-modifiable risk factors. It has been suggested that chronic inflammation may be involved in the development of prostate carcinogenesis. Therefore, our objective was to investigate the role of sexually and non-sexually transmitted infections in the occurrence of prostate cancer with a specific interest in the aggressive types based on data from EPICAP. Methods EPICAP is a population-based case-control study conducted in the département of Hérault, France, between 2012 and 2014. A total of 819 incident cases and 879 controls were interviewed face-to-face using a standardized questionnaire gathering information on known or suspected risk factors of prostate cancer and personal history of specific sexually and non-sexually transmitted infections: Gonorrhea, Syphilis, Trichomonas, Herpes, Mononucleosis, Epstein Barr, Varicella-zoster, and Dengue. Odds Ratios (OR) and their 95% confidence interval were estimated using multivariate unconditional logistic regression. Results No association emerged for the history of sexually transmitted infections (OR 1.04, 95%CI: 0.84-1.25) and non-sexually transmitted infections (OR1.09, 95%CI: 0.89-1.34) and the risk of prostate cancer. Even for all the infections studied separately, there was no association with the risk of low-grade or high-grade prostate cancer. Conclusions Our results showed that sexually or non-sexually transmitted infections do not seem to be risk factors for prostate cancer in the EPICAP study. Therefore, further investigation is needed to help advance our understanding of the role of chronic inflammation in the etiology of prostate cancer, with a particular focus on its most aggressive types.

Development and validation of a model for predicting the risk of prostate cancer.

Abnormal hematologic parameters before patients undergoing prostate biopsy play a pivotal role in guiding the surgical management of prostate cancer (PCa) incidence. This study aims to establish the first nomogram for predicting PCa risk for better surgical management. We retrospectively reviewed and analyzed the data including basic information, preoperative hematologic parameters, and imaging examination of 540 consecutive patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy for elevated prostate-specific antigen (PSA) in our medical center between 2017 and 2021. Logistic regression analysis was used to determine the risk factors for PCa occurrence, and the nomogram was constructed to predict PCa occurrence. Finally, the data including 121 consecutive patients in 2022 were prospectively collected to further verify the results. In retrospective analyses, univariate and multivariate logistic analyses identified that three variables including age, diabetes, and De Ritis ratio (aspartate transaminase/alanine transaminase, AST/ALT) were determined to be significantly associated with PCa occurrence. A nomogram was constructed based on these variables for predicting the risk of PCa, and a satisfied predictive accuracy of the model was determined with a C-index of 0.765, supported by a prospective validation group with a C-index of 0.736. The Decision curve analysis showed promising clinical application. In addition, our results also showed that the De Ritis ratio was significantly correlated with the clinical stage of PCa patients, including T, N, and M stages, but insignificantly related to the Gleason score. The increased De Ritis ratio was significantly associated with the risk and clinical stage of PCa and this nomogram with good discrimination could effectively improve individualized surgical management for patient underdoing prostate biopsy.

The functional roles of m6A modification in prostate cancer.

Prostate cancer (PCa) is the most prevalent malignancy of the male genitourinary system, and its etiology suggests that genetics is an essential risk factor for its development and progression, while exogenous factors may have an significant impact on this risk. Initial diagnosis of advanced PCa is relatively frequent, and androgen deprivation therapy (ADT) is the predominant standard of care for PCa and the basis for various novel combination therapy regimens, and is often required throughout the patient's subsequent treatment. Although diagnostic modalities and treatment options are evolving, some patients suffer from complications, including biochemical relapse, metastasis and treatment resistance. Mechanisms of PCa pathogenesis and progression have been the focus of research. N6-methyladenosine (m6A) is an RNA modification involved in cell physiology and tumor metabolism. It has been observed to affect the evolution of diverse cancers through the regulation of gene expression. Genes associated with m6A are prominent in PCa and are involved in multiple aspects of desmoresistant PCa occurrence, progression, PCa bone metastasis (BM), and treatment resistance. Here, we explore the role of m6A modifications in promoting PCa.

Unlocking the role of non-coding RNAs in prostate cancer progression: exploring the interplay with the Wnt signaling pathway.

Prostate cancer (PCa) is one of the most common cancers in males, exhibiting a wide spectrum of clinical manifestations that pose challenges in its diagnosis and treatment. The Wnt signaling pathway, a conserved and complex pathway, is crucial for embryonic development, tissue homeostasis, and various physiological processes. Apart from the classical Wnt/β-catenin signaling pathway, there exist multiple non-classical Wnt signaling pathways, including the Wnt/PCP and Wnt/Ca2+ pathways. Non-coding RNAs (ncRNAs) are involved in the occurrence and development of PCa and the response to PCa treatment. ncRNAs are known to execute diverse regulatory roles in cellular processes, despite their inability to encode proteins. Among them, microRNAs, long non-coding RNAs, and circular RNAs play key roles in the regulation of the Wnt signaling pathway in PCa. Aberrant expression of these ncRNAs and dysregulation of the Wnt signaling pathway are one of the causes of cell proliferation, apoptosis, invasion, migration, and angiogenesis in PCa. Moreover, these ncRNAs affect the characteristics of PCa cells and hold promise as diagnostic and prognostic biomarkers. Herein, we summarize the role of ncRNAs in the regulation of the Wnt signaling pathway during the development of PCa. Additionally, we present an overview of the current progress in research on the correlation between these molecules and clinical features of the disease to provide novel insights and strategies for the treatment of PCa.