-
Sensors (Basel, Switzerland) Feb 2022Prostate cancer, which is also known as prostatic adenocarcinoma, is an unconstrained growth of epithelial cells in the prostate and has become one of the leading causes...
Prostate cancer, which is also known as prostatic adenocarcinoma, is an unconstrained growth of epithelial cells in the prostate and has become one of the leading causes of cancer-related death worldwide. The survival of patients with prostate cancer relies on detection at an early, treatable stage. In this paper, we introduce a new comprehensive framework to precisely differentiate between malignant and benign prostate cancer. This framework proposes a noninvasive computer-aided diagnosis system that integrates two imaging modalities of MR (diffusion-weighted (DW) and T2-weighted (T2W)). For the first time, it utilizes the combination of functional features represented by apparent diffusion coefficient (ADC) maps estimated from DW-MRI for the whole prostate in combination with texture features with its first- and second-order representations, extracted from T2W-MRIs of the whole prostate, and shape features represented by spherical harmonics constructed for the lesion inside the prostate and integrated with PSA screening results. The dataset presented in the paper includes 80 biopsy confirmed patients, with a mean age of 65.7 years (43 benign prostatic hyperplasia, 37 prostatic carcinomas). Experiments were conducted using different well-known machine learning approaches including support vector machines (SVM), random forests (RF), decision trees (DT), and linear discriminant analysis (LDA) classification models to study the impact of different feature sets that lead to better identification of prostatic adenocarcinoma. Using a leave-one-out cross-validation approach, the diagnostic results obtained using the SVM classification model along with the combined feature set after applying feature selection (88.75% accuracy, 81.08% sensitivity, 95.35% specificity, and 0.8821 AUC) indicated that the system's performance, after integrating and reducing different types of feature sets, obtained an enhanced diagnostic performance compared with each individual feature set and other machine learning classifiers. In addition, the developed diagnostic system provided consistent diagnostic performance using 10-fold and 5-fold cross-validation approaches, which confirms the reliability, generalization ability, and robustness of the developed system.
Topics: Adenocarcinoma; Aged; Diffusion Magnetic Resonance Imaging; Humans; Male; Prostate; Prostatic Neoplasms; Reproducibility of Results
PubMed: 35270995
DOI: 10.3390/s22051848 -
Cancer Epidemiology, Biomarkers &... Feb 2020
Topics: Global Burden of Disease; Humans; Incidence; Male; Mass Screening; Mortality; Prostate; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Risk Assessment; Risk Factors
PubMed: 32024765
DOI: 10.1158/1055-9965.EPI-19-0412 -
Archives of Pathology & Laboratory... Mar 2020The incidence of neuroendocrine tumors of the prostate increases after hormonal therapy. Neuroendocrine tumors possess a broad spectrum of morphologic features and pose... (Review)
Review
CONTEXT.—
The incidence of neuroendocrine tumors of the prostate increases after hormonal therapy. Neuroendocrine tumors possess a broad spectrum of morphologic features and pose challenges in the pathologic diagnosis and clinical management of patients.
OBJECTIVE.—
To present a brief updated summary of neuroendocrine tumors of the prostate with an overview of their histopathologic and immunohistochemical profiles and differential diagnoses.
DATA SOURCES.—
Literature review, personal experience in the daily practice of pathologic diagnosis, and laboratory research.
CONCLUSIONS.—
Our understanding of neuroendocrine tumors of the prostate classification and diagnosis continues to evolve. These advances benefit the risk stratification and management of prostate cancer.
Topics: Adenocarcinoma; Chromogranin A; Diagnosis, Differential; Humans; Immunohistochemistry; Male; Neuroendocrine Tumors; Prostate; Prostatic Neoplasms; Receptors, Androgen; Synaptophysin
PubMed: 31644322
DOI: 10.5858/arpa.2019-0434-RA -
BMC Medicine Jul 2022Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially...
BACKGROUND
Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort.
METHODS
This study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients' prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method.
RESULTS
The median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score≥21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4-5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort.
CONCLUSIONS
M1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.
Topics: Adenocarcinoma; Carcinoma, Intraductal, Noninfiltrating; Homologous Recombination; Humans; Male; Prostate; Prostatic Neoplasms
PubMed: 35864546
DOI: 10.1186/s12916-022-02430-0 -
Journal of Enzyme Inhibition and... Dec 2023Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) protein tyrosine kinases co-expressed in various cancers such as ovarian,...
Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) protein tyrosine kinases co-expressed in various cancers such as ovarian, breast, colon, and prostate subtypes. Herein, new TAK-285 derivatives (-) were synthesised, characterised, and biologically evaluated as dual EGFR/HER2 inhibitors. Compound exhibited IC values of 2.3 nM over EGFR and 234 nM over HER2, which is 38-fold of staurosporine and 10-fold of TAK-285 over EGFR. Compound also showed high selectivity profile when tested over a small kinase panel. Compounds - showed IC values in the range of 1.0-7.3 nM and 0.8-2.8 nM against PC3 and 22RV1 prostate carcinoma cell lines, respectively. Cell cycle analysis, apoptotic induction, molecular docking, dynamics, and MM-GBSA studies confirmed the plausible mechanism(s) of compound as a potent EGFR/HER2 dual inhibitor with an effective antiproliferative action against prostate carcinoma.
Topics: Male; Humans; Molecular Docking Simulation; Prostate; Cell Line, Tumor; Antineoplastic Agents; Prostatic Neoplasms; Carcinoma; Protein Kinase Inhibitors; Cell Proliferation; Structure-Activity Relationship; Drug Screening Assays, Antitumor; Molecular Structure; ErbB Receptors
PubMed: 37096560
DOI: 10.1080/14756366.2023.2202358 -
Journal of Cancer Research and Clinical... Jul 2022Rapid evolution of the therapeutic management of prostate cancer, especially in in second-generation androgen inhibitors, has increased the opportunity of transformation... (Review)
Review
BACKGROUND
Rapid evolution of the therapeutic management of prostate cancer, especially in in second-generation androgen inhibitors, has increased the opportunity of transformation from prostate cancer (PCa) to neuroendocrine prostate cancer (NEPC). NEPC still lacks effective diagnostic and therapeutic interventions. Researches into the molecular characteristics of neuroendocrine differentiation is undoubtedly crucial to the discovery of new target genes for accurate diagnostic and therapeutic targets.
PURPOSE
In this review, we focus on the relevant genes and molecular mechanisms that have contributed to the transformation in the progression of PCa and discuss the potential targeted molecule that might improve diagnostic accuracy and therapeutic effectiveness.
METHODS
The relevant literatures from PubMed have been reviewed for this article.
CONCLUSION
Several molecular characteristics influence the progression of neuroendocrine differentiation of prostate cancer which will provide a novel sight for accurate diagnosis and target therapeutic intervention for patients with NEPC.
Topics: Carcinoma, Neuroendocrine; Cell Line, Tumor; Disease Progression; Humans; Male; Prostate; Prostatic Neoplasms
PubMed: 35633416
DOI: 10.1007/s00432-022-04061-7 -
Cells Apr 2020The term aggressive variant prostate cancer (AVPCa) refers to androgen receptor (AR)-independent anaplastic forms of prostate cancer (PCa), clinically characterized by a... (Review)
Review
The term aggressive variant prostate cancer (AVPCa) refers to androgen receptor (AR)-independent anaplastic forms of prostate cancer (PCa), clinically characterized by a rapidly progressive disease course. This involves hormone refractoriness and metastasis in visceral sites. Morphologically, AVPCa is made up of solid sheets of cells devoid of pleomorphism, with round and enlarged nuclei with prominent nucleoli and slightly basophilic cytoplasm. The cells do not show the typical architectural features of prostatic adenocarcinoma and mimic the undifferentiated carcinoma of other organs and locations. The final diagnosis is based on the immunohistochemical expression of markers usually seen in the prostate, such as prostate-specific membrane antigen (PSMA). A subset of AVPCa can also express neuroendocrine (NE) markers such as chromogranin A, synaptophysin and CD56. This letter subset represents an intermediate part of the spectrum of NE tumors which ranges from small cell to large cell carcinoma. All such tumors can develop following potent androgen receptor pathway inhibition. This means that castration-resistant prostate cancer (CRPCa) transdifferentiates and becomes a treatment-related NE PCa in a clonally divergent manner. The tumors that do not show NE differentiation might harbor somatic and/or germline alterations in the DNA repair pathway. The identification of these subtypes has direct clinical relevance with regard to the potential benefit of platinum-based chemotherapy, poly (ADP-ribose) polymerase inhibitors and likely further therapies.
Topics: Carcinoma, Neuroendocrine; Humans; Male; Prostate; Prostatic Neoplasms; Receptors, Androgen
PubMed: 32344931
DOI: 10.3390/cells9051073 -
Nature Communications Jun 2021Despite advances in the development of highly effective androgen receptor (AR)-directed therapies for the treatment of men with advanced prostate cancer, acquired...
Despite advances in the development of highly effective androgen receptor (AR)-directed therapies for the treatment of men with advanced prostate cancer, acquired resistance to such therapies frequently ensues. A significant subset of patients with resistant disease develop AR-negative tumors that lose their luminal identity and display neuroendocrine features (neuroendocrine prostate cancer (NEPC)). The cellular heterogeneity and the molecular evolution during the progression from AR-positive adenocarcinoma to AR-negative NEPC has yet to be characterized. Utilizing a new genetically engineered mouse model, we have characterized the synergy between Rb1 loss and MYCN (encodes N-Myc) overexpression which results in the formation of AR-negative, poorly differentiated tumors with high metastatic potential. Single-cell-based approaches revealed striking temporal changes to the transcriptome and chromatin accessibility which have identified the emergence of distinct cell populations, marked by differential expression of Ascl1 and Pou2f3, during the transition to NEPC. Moreover, global DNA methylation and the N-Myc cistrome are redirected following Rb1 loss. Altogether, our data provide insight into the progression of prostate adenocarcinoma to NEPC.
Topics: Adenocarcinoma; Animals; Carcinoma, Neuroendocrine; Cell Line, Tumor; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Male; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; N-Myc Proto-Oncogene Protein; Organ Culture Techniques; Prognosis; Prostate; Prostatic Neoplasms; Receptors, Androgen; Retinoblastoma Protein; Mice
PubMed: 34099734
DOI: 10.1038/s41467-021-23780-y -
The Prostate Jan 2022Metabolic reprograming is now a recognized hallmark of cancer. The prostate-specific phosphatase and tensin homolog deleted on chromosome 10 (Pten) gene-conditional...
BACKGROUND
Metabolic reprograming is now a recognized hallmark of cancer. The prostate-specific phosphatase and tensin homolog deleted on chromosome 10 (Pten) gene-conditional knockout (KO) mouse carcinogenesis model is highly desirable for studying prostate cancer biology and prevention due to its close resemblance of primary molecular defects and histopathological features of human prostate cancer. We have recently published macromolecular profiling of this model by proteomics and transcriptomics, denoting a preeminence of inflammation and myeloid suppressive immune cell features. Here, we performed metabolomic analyses of Pten-KO prostate versus wild type (WT) counterpart for discernable changes in the aqueous metabolites and contrasted to those in the TRAMP neuroendocrine carcinoma (NECa).
METHODS
Three matched pairs of tissue-specific conditional Pten-KO mouse prostate and WT prostate of litter/cage-mates at 20-22 weeks of age and three pairs of TRAMP NECa versus WT (28-31 weeks) were profiled for their global aqueous metabolite changes, using hydrophilic interaction liquid chromatography-tandem mass spectrometry.
RESULTS
The Pten-KO prostate increased purine nucleotide pools, cystathionine, and both reduced and oxidized glutathione (GSH, GSSG), and gluconate/glucuronate species in addition to cholesteryl sulfate and polyamine precursor ornithine. On the contrary, Pten-KO prostate contained diminished pools of glycolytic intermediates and phosphorylcholine derivatives, select amino acids, and their metabolites. Bioinformatic integration revealed a significant shunting of glucose away from glycolysis-citrate cycle and glycerol-lipid genesis to pentose phosphate cycle for NADPH/GSH/GSSG redox and pentose moieties for purine and pyrimidine nucleotides, and glycosylation/glucuronidation. Implicit arginine catabolism to ornithine was consistent with immunosuppression in Pten-KO model. While also increased in cystathionine-GSH/GSSG, purine, and pyrimidine nucleotide pools and glucuronidation at the expense of glycolysis-citrate cycle, the TRAMP NECa increased abundance of many amino acids, methyl donor S-adenosyl-methionine, and intermediates for phospholipids without increasing cholesteryl sulfate or ornithine.
CONCLUSIONS
The aqueous metabolomic patterns in Pten-KO prostate and TRAMP NECa shared similarities in the greater pools of cystathionine, GSH/GSSG redox pair, and nucleotides and shunting away from glycolysis-citrate cycle in both models. Remarkable metabolic distinctions between them included metabolisms of many amino acids (protein synthesis; arginine-ornithine/immune suppression) and cholesteryl sulfate and methylation donor for epigenetic regulations.
Topics: Animals; Biomarkers; Carcinoma, Neuroendocrine; Chromatography, Liquid; Disease Models, Animal; Male; Metabolomics; Mice; Mice, Knockout; PTEN Phosphohydrolase; Prostate; Prostatic Neoplasms; Receptors, Tumor Necrosis Factor, Member 25; Tandem Mass Spectrometry
PubMed: 34662447
DOI: 10.1002/pros.24256 -
Endocrine-related Cancer Dec 2015Research in the area of stem/progenitor cells has led to the identification of multiple stem-like cell populations implicated in prostate homeostasis and cancer... (Review)
Review
Research in the area of stem/progenitor cells has led to the identification of multiple stem-like cell populations implicated in prostate homeostasis and cancer initiation. Given that there are multiple cells that can regenerate prostatic tissue and give rise to prostate cancer, our focus should shift to defining the signaling mechanisms that drive differentiation and progenitor self-renewal. In this article, we will review the literature, present the evidence and raise important unanswered questions that will help guide the field forward in dissecting critical mechanisms regulating stem-cell differentiation and tumor initiation.
Topics: Adenocarcinoma; Androgens; Animals; Cell Culture Techniques; Cell Differentiation; Cell Lineage; Cell Self Renewal; Cell Transformation, Neoplastic; Cells, Cultured; Epithelium; Homeostasis; Humans; Male; Mesenchymal Stem Cells; Mice; Models, Animal; Models, Biological; Multipotent Stem Cells; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Neoplastic Stem Cells; Orchiectomy; Paracrine Communication; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Androgen; Signal Transduction; Stem Cell Niche; Stromal Cells
PubMed: 26307022
DOI: 10.1530/ERC-15-0195