Tissue-Based Biomarkers for the Risk Stratification of Men With Clinically Localized Prostate Cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Basourakos SP
PROVIDER: S-EPMC8193839 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Obesity is associated with an increased risk of fatal prostate cancer. We aimed to elucidate the importance and relevant timing of obesity and weight change for prostate cancer progression. We identified 5,158 men diagnosed with localized prostate cancer (clinical stage T1/T2) from 1986 to 2012 in the Health Professionals Follow-up Study. Men were followed for biochemical recurrence and lethal prostate cancer (development of distant metastasis or prostate cancer-specific mortality) until 2012. Cox regression estimated hazard ratios (HRs) for body mass index (BMI) at age 21, BMI at diagnosis, "long-term" weight change from age 21 to diagnosis and "short-term" weight change over spans of 4 and 8 years preceding diagnosis. Because weight, weight change and mortality are strongly associated with smoking, we repeated analyses among never smokers only (N?=?2,559). Among all patients, neither weight change nor BMI (at age 21 or at diagnosis) was associated with lethal prostate cancer. Among never smokers, long-term weight gain was associated with an increased risk of lethal disease (HR for gaining >30 pounds vs. stable weight [±10 pounds] 1.59, 95% CI, 1.01-2.50, p-trend?=?0.06). Associations between weight change, BMI and lethal prostate cancer were stronger for men with BMI???25 at age 21 compared to those with BMI?<?25. Weight change and obesity were not associated with an increased risk of biochemical recurrence. Our findings among never smoker men diagnosed with localized prostate cancer suggest a positive association between long-term weight gain and risk of lethal prostate cancer. Metabolic changes associated with weight gain may promote prostate cancer progression.
| S-EPMC5518616 | biostudies-literature
Project description:In localized prostate cancer clinicopathologic variables have been used to develop prognostic nomograms quantifying the probability of locally advanced disease, of pelvic lymph node and distant metastasis at diagnosis or the probability of recurrence after radical treatment of the primary tumor. These tools although essential in daily clinical practice for the management of such a heterogeneous disease, which can be cured with a wide spectrum of treatment strategies (i.e., active surveillance, RP and radiation therapy), do not allow the precise distinction of an indolent instead of an aggressive disease. In recent years, several prognostic biomarkers have been tested, combined with the currently available clinicopathologic prognostic tools, in order to improve the decision-making process. In the following article, we reviewed the literature of the last 10 years and gave an overview report on commercially available tissue-based biomarkers and more specifically on mRNA-based gene expression classifiers. To date, these genomic tests have been widely investigated, demonstrating rigorous quality criteria including reproducibility, linearity, analytical accuracy, precision, and a positive impact in the clinical decision-making process. Albeit data published in literature, the systematic use of these tests in prostate cancer is currently not recommended due to insufficient evidence.
| S-EPMC8781984 | biostudies-literature
Project description:Although prostate cancer (PCa) is the most commonly diagnosed cancer in men, most patients do not die from the disease. Prostate specific antigen (PSA), the most widely used oncologic biomarker, has revolutionized screening and early detection, resulting in reduced proportion of patients presenting with advanced disease. However, given the inherent limitations of PSA, additional diagnostic and prognostic tools are needed to facilitate early detection and accurate risk stratification of disease. Serum, urine, and tissue-based biomarkers are increasingly being incorporated into the clinical care paradigm, but there is still a limited understanding of how to use them most effectively. In the current article, we review test characteristics and clinical performance data for both serum [4 K score, prostate health index (phi)] and urine [SelectMDx, ExoDx Prostate Intelliscore, MyProstateScore (MPS), and PCa antigen 3 (PCA3)] biomarkers to aid decisions regarding initial or repeat biopsies as well as tissue-based biomarkers (Confirm MDx, Decipher, Oncotype Dx, and Polaris) aimed at risk stratifying patients and identifying those patients most likely to benefit from treatment versus surveillance or monotherapy versus multi-modal therapy.
| S-EPMC9201356 | biostudies-literature
Project description:BackgroundProstate cancer in African American (AA) men has a poor prognosis. This study aimed to identify potential genetic risk factors for prostate cancer in AA men.MethodsWe used prostate cancer tissue from 61 patients who underwent radical prostatectomy. We compared somatic gene expression in Caucasian (CA) and AA men using RNA sequencing.ResultsBy comparing the RNA-seq data obtained from prostate cancer tissue between AA and CA men, this study showed a significant difference in expression levels of 45 genes. Pathway analysis of 45 genes using Kyoto Encyclopedia of Genes and Genomesenrichment analysis revealed a neuroactive ligand-receptor interaction signal. In addition, the results of the Ingenuity Pathway Analysis showed pathways involved sphingosine-1-phosphate signaling. Furthermore, validating 45 genes in the The Cancer Genome Atlas (TCGA) Provisional cohort, cholinergic receptor muscarinic 3 expression level was significantly lower in AA than in CA men, and the results showed a significantly higher rate of biochemical recurrence in patients with low expression.ConclusionsWe identified genetic differences of clinically localized prostate cancer in AAs and CAs by RNA sequencing.
| S-EPMC8498718 | biostudies-literature
Project description:PurposeRacial differences in prostate cancer treatment patterns have motivated concerns about over- and undertreatment. We surveyed black and white patients with localized prostate cancer (LPC) regarding their treatment decision-making processes to gain a better perspective on factors associated with LPC treatment choice.MethodsWe conducted a population-based, cross-sectional survey of 260 men (132 black, 128 white) aged ≤75 years, with newly diagnosed LPC. Our primary outcome was treatment choice (either surgery, radiation, or watchful waiting/active surveillance (WW/AS)), and our primary predictors were race and tumor risk level.ResultsOverall, treatment choice did not differ by race. As cancer risk increased, both black and white patients were more likely to undergo surgery and less likely to receive radiation. However, the pattern of WW/AS was different between white and black men. White men were less likely to select WW/AS as cancer risk increased, while risk level was unrelated to black men undergoing WW/AS. Urologist's recommendation had the greatest impact on men's treatment choice, followed by tumor risk level, age, and personal preferences.ConclusionsAlthough there were no overall racial differences in treatment choice, when stratified by tumor risk level, the pattern of WW/AS was different between white and black patients, suggesting that over- and undertreatment is a larger concern for black than white men. A risk-stratified approach to understand racial disparities in LPC treatment and better strategies to aid black men in their treatment decision-making are needed to reduce racial disparities in prostate cancer outcomes.
| S-EPMC8404160 | biostudies-literature
Project description:Prognostic biomarkers are needed to distinguish patients with clinically localized prostate cancer (PCa) who are at high risk of metastatic progression. The tumor transcriptome may reveal its aggressiveness potential and have utility for predicting adverse patient outcomes. Genomewide gene expression levels were measured in primary tumor samples of 383 patients in a population-based discovery cohort, and from an independent clinical validation dataset of 78 patients. Patients were followed for ≥ 5 years after radical prostatectomy to ascertain outcomes. Area under the receiver-operating characteristic curve (AUC), partial AUC (pAUC, 95% specificity), and P-value criteria were used to detect and validate the differentially expressed transcripts. Twenty-three differentially expressed transcripts in patients with metastatic-lethal compared with nonrecurrent PCa were validated (P < 0.05; false discovery rate < 0.20) in the independent dataset. The addition of each validated transcript to a model with Gleason score showed that 17 transcripts significantly improved the AUC (range: 0.83-0.88; all P-values < 0.05). These differentially expressed mRNAs represent genes with diverse cellular functions related to tumor aggressiveness. This study validated 23 gene transcripts for predicting metastatic-lethal PCa in patients surgically treated for clinically localized disease. Several of these mRNA biomarkers have clinical potential for identifying the subset of PCa patients with more aggressive tumors who would benefit from closer monitoring and adjuvant therapy.
| S-EPMC5510189 | biostudies-literature
Project description:Gleason grading is an important prognostic indicator for prostate adenocarcinoma and is crucial for patient treatment decisions. However, intermediate-risk patients diagnosed in Gleason Grade Groups (GG) 2 and GG3 can harbour either aggressive or non-aggressive disease, resulting in under- or over-treatment of a significant number of patients. Here, we performed proteomic, differential expression, machine learning, and survival analyses for 1,348 matched tumour and benign samples from 278 patients. Three proteins (F5, TMEM126B and EARS2) were identified as candidate biomarkers in patients with biochemical recurrence. Multivariate Cox regression yielded 18 proteins, from which a risk score was constructed to dichotomise prostate cancer patients into low- and high-risk groups. This 18-protein signature is prognostic for the risk of biochemical recurrence and completely independent of the intermediate GG. Our results suggest that markers generated by computational proteomic profiling have the potential for clinical applications including integration into prostate cancer management.
2023-11-30 | PXD041005 | Pride
Project description:PurposeCyclooxygenase-2 (COX-2) is a potential pharmacologic target for the prevention of various malignancies, including prostate cancer. We conducted a randomized, double-blind trial to examine the effect of celecoxib on drug-specific biomarkers from prostate tissue obtained at prostatectomy.Patients and methodsPatients with localized prostate cancer and Gleason sum > or = 7, prostate-specific antigen (PSA) > or = 15 ng/mL, clinical stage T2b or greater, or any combination with greater than 45% risk of capsular penetration were randomly assigned to celecoxib 400 mg by mouth twice daily or placebo for 4 to 6 weeks before prostatectomy. The primary end point was the difference in prostatic prostaglandin levels between the two groups. Secondary end points were differences in COX-1 and -2 expressions; oxidized DNA bases; and markers of proliferation, apoptosis and angiogenesis. Tissue celecoxib concentrations also were measured. Tertiary end points were drug safety and compliance.ResultsSeventy-three patients consented, and 64 were randomly assigned and included in the intention-to-treat analysis. There were no treatment differences in any of the primary or secondary outcomes. Multivariable regression revealed that tumor tissue had significantly lower COX-2 expression than benign prostatic tissue (P = .01) and significantly higher levels of the proliferation marker Ki-67 (P < .0001). Celecoxib was measurable in prostate tissue of patients on treatment, demonstrating that celecoxib reached its target. Celecoxib was safe and resulted in only grade 1 toxicities.ConclusionTreatment with 4 to 6 weeks of celecoxib had no effect on intermediate biomarkers of prostate carcinogenesis, despite the achievement of measurable tissue levels. We caution against using celecoxib 400 mg twice daily as a preventive agent for prostate cancer in additional studies.
| S-EPMC2799055 | biostudies-literature
Project description:Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer.
| S-EPMC5549774 | biostudies-other
Project description:To examine the effect of socioeconomic factors on survival in black and white patients with local or regional prostate cancer.All cases (n = 2046) of clinically localized prostate cancer diagnosed from 1990 to 2000 at the Henry Ford Health System and the Henry Ford Medical Group, equal access health centers, were included. Data on the stage, grade, age at diagnosis, socioeconomic status, treatment given, comorbidities, and vital statistics were gathered from the Henry Ford Medical Group tumor registry and computerized databases, pathologic reports, patient charts, Surveillance, Epidemiology, and End Results database, and the national death registry. The endpoints were the overall and cancer-specific survival. Survival was calculated using Cox proportional hazards regression models.Of the 2046 cases, 1243 were white and 803 were black. Black patients were more likely to have lower incomes, a greater baseline prostate-specific antigen level, and greater comorbidities. They were also more likely to undergo radiotherapy and less likely to undergo radical prostatectomy. Univariate analysis, with white race as the baseline hazard, showed that black patients had significantly increased cancer-specific (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.01-2.13) and overall (HR 1.29, 95% CI 1.09-1.53) mortality. However, adjusting for insurance status and income on multivariate analysis revealed no significant differences in cancer-specific (HR 1.04, 95% CI 0.66-1.64) and overall (HR 0.96, 95% CI 0.78-1.18) survival.In this cohort, socioeconomic factors were sufficient to explain the disparity in survival between white and black patients. Survival differences disappeared after adjusting for income status on multivariate analysis.
| S-EPMC5557082 | biostudies-other