A study protocol to characterise pathophysiological and molecular markers of rheumatic heart disease and degenerative aortic stenosis using multiparametric cardiovascular imaging and multiomics techniques.

INTRODUCTION: Rheumatic heart disease (RHD), degenerative aortic stenosis (AS), and congenital valve diseases are prevalent in sub-Saharan Africa. Many knowledge gaps remain in understanding disease mechanisms, stratifying phenotypes, and prognostication. Therefore, we aimed to characterise patients through clinical profiling, imaging, histology, and molecular biomarkers to improve our understanding of the pathophysiology, diagnosis, and prognosis of RHD and AS. METHODS: In this cross-sectional, case-controlled study, we plan to recruit RHD and AS patients and compare them to matched controls. Living participants will undergo clinical assessment, echocardiography, CMR and blood sampling for circulatory biomarker analyses. Tissue samples will be obtained from patients undergoing valve replacement, while healthy tissues will be obtained from cadavers. Immunohistology, proteomics, metabolomics, and transcriptome analyses will be used to analyse circulatory- and tissue-specific biomarkers. Univariate and multivariate statistical analyses will be used for hypothesis testing and identification of important biomarkers. In summary, this study aims to delineate the pathophysiology of RHD and degenerative AS using multiparametric CMR imaging. In addition to discover novel biomarkers and explore the pathomechanisms associated with RHD and AS through high-throughput profiling of the tissue and blood proteome and metabolome and provide a proof of concept of the suitability of using cadaveric tissues as controls for cardiovascular disease studies.

Nephroprotective and anti-inflammatory potential of aqueous extract from Persea americana seeds against cadmium-induced nephrotoxicity in Wistar rats.

Cadmium is a toxic metal and poses a high environmental risk to animals and humans, alike. It is thus pertinent to search for medicinal plants in protecting against cadmium toxicity. This study aims at investigating the ability of aqueous extract of Persea americana seeds (AEPA) in ameliorating the toxic effects of cadmium in the kidneys of cadmium-exposed Wistar rats. Male Wistar rats were grouped into five, of six animals each. Different groups of animals received normal saline (control group), 200 mg/kg body weight AEPA, 400 mg/kg AEPA, and standard drug, Livolin Forte, respectively. A last group of animals was left untreated. To induce toxicity, all animals, except the control group, were exposed to cadmium (200 mg/L, as CdCl2) in their main drinking water for 21 days. Biochemical analysis of serum kidney markers, oxidative stress and antioxidant status, as well as anti-inflammatory activities, was done using standard methods and kits. In silico analysis was performed on phytochemicals reported to be abundant in AEPA. Treatment with 400 mg/kg AEPA significantly reversed (P ≤ 0.05) the adverse effect of cadmium on serum creatinine, urea, uric acid and blood urea nitrogen, and restored (P ≤ 0.05) antioxidant status, evidenced by its significant effect on superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, reduced glutathione, and lipid peroxidation activities. AEPA, at 400 mg/kg also exhibited significant anti-inflammatory effects, which was shown by reduced interleukin-2 and tumour necrosis factor α activities. Molecular docking of phytochemicals with the selected protein target also confirmed the therapeutic potential of AEPA. The study concluded that aqueous extract of AEPA protects against cadmium-induced kidney toxicity and inflammation.

Bioactive compounds and their libraries: An insight into prospective phytotherapeutics approach for oral mucocutaneous cancers.

Oral mucocutaneous cancers (OMCs) are cancers that affect both the oral mucosa and perioral cutaneous structures. Common OMCs are squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and malignant melanoma (MM). Anatomical similarities and conventions which categorizes these lesions blur the magnitude of OMCs in diverse populations. The burden of OMC is high in the sub-Saharan Africa and Indian subcontinents, and the cost of management is prohibitive in the resource-limited, developing world. Hence, there is a pressing demand for the use of cost-effective in silico approaches to identify diagnostic tools and treatment targets for diseases with high burdens in these regions. Due to their ubiquitousness and accessibility, the use of therapeutic efficacy of plant bioactive compounds in the management of OMC is both appropriate and plausible. Furthermore, screening known mechanistic disease targets with well annotated plant bioactive compound libraries is poised to improve the routine management of OMCs provided that the requisite access to database resources are available and accessible. Using natural products minimizes the side effects and morbidities associated with conventional therapies. The development of innovative treatments approaches would tremendously benefit the African and Indian populace and reduce the mortalities associated with OMCs in the developing world. Hence, we discuss herein, the potential benefits, opportunities and challenges of using bioactive compound libraries in the management of OMCs.

Antibody-Based Targeted Interventions for the Diagnosis and Treatment of Skin Cancers.

BACKGROUND: Cutaneous malignancies most commonly arise from skin epidermal cells. These cancers may rapidly progress from benign to a metastatic phase. Surgical resection represents the gold standard therapeutic treatment of non-metastatic skin cancer while chemo- and/or radiotherapy are often used against metastatic tumors. However, these therapeutic treatments are limited by the development of resistance and toxic side effects, resulting from the passive accumulation of cytotoxic drugs within healthy cells. OBJECTIVE: This review aims to elucidate how the use of monoclonal Antibodies (mAbs) targeting specific Tumor Associated Antigens (TAAs) is paving the way to improved treatment. These mAbs are used as therapeutic or diagnostic carriers that can specifically deliver cytotoxic molecules, fluorophores or radiolabels to cancer cells that overexpress specific target antigens. RESULTS: mAbs raised against TAAs are widely in use for e.g. differential diagnosis, prognosis and therapy of skin cancers. Antibody-Drug Conjugates (ADCs) particularly show remarkable potential. The safest ADCs reported to date use non-toxic photo-activatable Photosensitizers (PSs), allowing targeted Photodynamic Therapy (PDT) resulting in targeted delivery of PS into cancer cells and selective killing after light activation without harming the normal cell population. The use of near-infrared-emitting PSs enables both diagnostic and therapeutic applications upon light activation at the specific wavelengths. CONCLUSION: Antibody-based approaches are presenting an array of opportunities to complement and improve current methods employed for skin cancer diagnosis and treatment.

Prospects of nanodentistry for the diagnosis and treatment of maxillofacial pathologies and cancers.

Despite the commendable milestones achieved in molecular maxillofacial pathology in the last decade, there remains a paucity of utilization of ancillary nanomolecular tools that complement the omics-based approaches. As the advent of omics science transforms our understanding of tumour biology from a phenomenological to a complex network (systems-oriented) paradigm, several ancillary tools have emerged to improve the scope of individualized medicine. Targeted nano drug delivery systems have significantly reduced toxicity of chemotherapeutic agents in a precise manner. Many conventional cancer therapies are limited in efficacy and this has led to the emergence of nanomedical innovations. Despite the success of nanomedicine, a major challenge that persists is tumour heterogeneity and biological complexity. A good understanding of the interaction between inorganic nanoparticles and the biological systems has led to the development of better tools for individualized medicine. Tools such as the composite organic-inorganic nanoparticles (COINs) and the quantum dots (QD) have significantly improved the identification and quantification of disease biomarkers, histopathological detection methods, as well as improving the clinical translation and utility of these nanomaterials. Nanomedicine has lent credence to several multipronged theranostic applications in medicine, and this has improved the medical practice tremendously. Despite the palpable influence of nanomedicine on the delivery of individualized medical therapies, the term "nanodentistry" remains in the background without much hype, albeit some progress has been made in this area. Hence, this review discusses the potential and challenges of nanodentistry in the diagnosis and treatment of maxillofacial pathologies, particularly cancer in resource-limited settings.

Destruction of the stem cell Niche, Pathogenesis and Promising Treatment Targets for Primary Scarring Alopecias.

The Primary Scarring Alopecias are characterised by the irreversible destruction and fibrosis of hair follicles, leading to permanent and often disfiguring loss of hair. The pathophysiology of these diseases is not well understood. However, follicular-fibrosis and loss of the stem-cell niche appears to be a common theme. This review explores the pathogenesis of primary scarring alopecias, asking what happens to the stem cells of the hair follicle and how they may contribute to the progression of these diseases. Bulge-resident cells are lost (leading to loss of capacity for hair growth) from the follicle either by inflammatory-mediate apoptosis or through epigenetic reprogramming to assume a mesenchymal-like identity. What proportion of bulge cells is lost to which process is unknown and probably differs depending on the individual PCA and its specific inflammatory cell infiltrate. The formation of fibroblast-like cells from follicular stem cells may also mean that the cells of the bulge have a direct role in the pathogenesis. The identification of specific cells involved in the pathogenesis of these diseases could provide unique diagnostic and therapeutic opportunities to prevent disease progression by preventing EMT and specific pro-fibrotic signals.

The need for nationally accepted guidelines for undergraduate nuclear medicine teaching in MBChB programmes in South Africa.

According to the South African Health Professions Act No. 56 of 1974, specific skills outcomes of MBChB programmes are that a medical graduate must be able to utilise diagnostic aids, interpret findings and make diagnoses. Imaging techniques are an integral part of the numerous diagnostic and therapeutic aids used in contemporary medical practice; however, in South Africa, no formal directives exist to guide programme directors or nuclear medicine departments regarding an appropriate undergraduate nuclear medicine educational module. As of 2013, six South African schools of medicine are involved in undergraduate nuclear medicine teaching, in which it forms part of clinical modules taught at varying stages in the academic curriculum. Against this backdrop is the inequitable distribution of nuclear medicine resources, training facilities and staffing in the local state health sector. Inadequate undergraduate teaching and provincial differences in nuclear medicine service provision suggest that many clinicians and graduating medical students are unaware of how radionuclide techniques can facilitate patient management. This high level of imaging illiteracy has been associated with lack of patient referral, poor quality and inadequate referral, poor knowledge of radiation doses and poor awareness of radiation risks. Here we highlight the challenges of undergraduate nuclear medicine teaching in South Africa, emphasising the need for the implementation of guidelines for undergraduate nuclear medicine education. Employing nationally accepted guidelines for undergraduate nuclear medicine teaching in South African MBChB programmes will contribute to the effective utilisation of nuclear medicine and molecular imaging as a diagnostic and therapeutic modality by newly qualified medical practitioners.

No difference in the proteome of racially and geometrically classified scalp hair sample from a South African cohort: Preliminary findings.

Differences in the physiological proteome of men of different racial origin is poorly researched, albeit hair is mostly composed of keratins and keratin-associated proteins. Hence, we have carried out label-free, shotgun proteomics analysis on hair samples collected from black African, Caucasian, Asian, and Mixed-Ancestry donors within a heterogeneous population of the Western Cape of South Africa. Further, the same hair was also classified using geometrical measurements. Using both qualitative and quantitative proteomics bioinformatics pipelines, we identified over 450 protein groups (FDR = 0.01). Identified protein classes included keratins, keratin-associated proteins, histone proteins and desmosomes, inter alia. No protein by quantitative proteomic analyses significantly differentiated racial or geometric groups in our cohort. Functional pathway analysis of top-ranking proteins showed enrichment for skin, epidermal and tissue development, as well as intermediate-filament organization. Racial classification is a social construct, and attributing differences in a biologic endpoint to it is both imprecise and valueless in the era of precision medicine. Nonetheless, clarity on the physiological hair proteome could serve as a foundation for using hair proteomics for disease biomarker and targeted therapy identification for precision medicine. For the first time, we established the physiological hair proteome of individuals in a culturally diverse cohort from Africa. SIGNIFICANCE: For the first time we have been able to characterize the physiological human hair proteome in a culturally diverse South African cohort. We have also identified that proteomics differences were not observed in individual hair samples using our quantitative proteomics bioinformatics pipeline. This outcome supports a widely known notion that DNA sequence comparison often shows that people on each continent are not more genetically similar to one another than to people who come from other continents and that there is more genetic variation in Africa. Hence, adaptive traits such as hair and skin phenotype are not scientifically valid distinctions. Racial classification is believed to be a social construct, and attributing differences in a biologic endpoint to it is both imprecise and valueless in the era of precision medicine. Our preliminary finding would serve as a much-needed foundation for establishing a well-annotated, customized hair proteomics repository for Africans.

Pattern of distribution of reactive localised hyperplasia of the oral cavity in patients at a tertiary health institution in Nigeria.

BACKGROUND: Reactive localized hyperplastic lesions of the oral cavity (RHLs) are relatively common peripheral lesions which present as a range of clinically similar lesions at dental centers. Diagnosis can be challenging if dentists are unfamiliar with their clinicopathological across various populations. OBJECTIVE: This study reviews the pattern of distribution of RHLs of the oral mucosa in a hospital- the Obafemi Awolowo University Teaching Hospital Complex (OAUTHC), Ile-Ife. MATERIALS AND METHODS: We reviewed 10 years data from the archives of the Department of Oral Maxillofacial Surgery and Oral Pathology, Obafemi Awolowo University, Nigeria. Information on RHLs were extracted and recorded on standardized data forms and analyzed using STATA. RESULTS: The most common lesions were pyogenic granuloma (43.7%) and focal fibrous hyperplasia (39.7%), respectively. RHLs were found to be more frequent in women (66.7%) than men (33.3%). The most common locations of involvement was the gingivae (84.6%), and lesions were more common in the 9-29 year age group and the mean age was 37.7 (±21.1) years. The relationship between age group and reactive lesions was however not statistically significant. CONCLUSION: The major benefit of this study is an improved knowledge of the frequency and distribution of oral reactive lesions in sub-Saharan Africa which may be highly beneficial when establishing a diagnosis and treatment plan in clinical practice.

Systems Biology Approaches and Precision Oral Health: A Circadian Clock Perspective.

A vast majority of the pathophysiological and metabolic processes in humans are temporally controlled by a master circadian clock located centrally in the hypothalamic suprachiasmatic nucleus of the brain, as well as by specialized peripheral oscillators located in other body tissues. This circadian clock system generates a rhythmical diurnal transcriptional-translational cycle in clock genes and protein expression and activities regulating numerous downstream target genes. Clock genes as key regulators of physiological function and dysfunction of the circadian clock have been linked to various diseases and multiple morbidities. Emerging omics technologies permits largescale multi-dimensional investigations of the molecular landscape of a given disease and the comprehensive characterization of its underlying cellular components (e.g., proteins, genes, lipids, metabolites), their mechanism of actions, functional networks and regulatory systems. Ultimately, they can be used to better understand disease and interpatient heterogeneity, individual profile, identify personalized targetable key molecules and pathways, discover novel biomarkers and genetic alterations, which collectively can allow for a better patient stratification into clinically relevant subgroups to improve disease prediction and prevention, early diagnostic, clinical outcomes, therapeutic benefits, patient's quality of life and survival. The use of "omics" technologies has allowed for recent breakthroughs in several scientific domains, including in the field of circadian clock biology. Although studies have explored the role of clock genes using circadiOmics (which integrates circadian omics, such as genomics, transcriptomics, proteomics and metabolomics) in human disease, no such studies have investigated the implications of circadian disruption in oral, head and neck pathologies using multi-omics approaches and linking the omics data to patient-specific circadian profiles. There is a burgeoning body of evidence that circadian clock controls the development and homeostasis of oral and maxillofacial structures, such as salivary glands, teeth and oral epithelium. Hence, in the current era of precision medicine and dentistry and patient-centered health care, it is becoming evident that a multi-omics approach is needed to improve our understanding of the role of circadian clock-controlled key players in the regulation of head and neck pathologies. This review discusses current knowledge on the role of the circadian clock and the contribution of omics-based approaches toward a novel precision health era for diagnosing and treating head and neck pathologies, with an emphasis on oral, head and neck cancer and Sjögren's syndrome.

Geriatric dentistry education and context in a selection of countries in 5 continents.

PURPOSE/AIM: To summarize and discuss how geriatric dentistry has been addressed in dental schools of different countries regarding to (1) teaching students at the predoctoral level; (2) advanced training, and (3) research. METHOD AND MATERIALS: A convenience sample of faculty members from a selection of high, upper-middle and lower-middle income countries were recruited to complete the survey. The survey had 5 open-ended main topics, and asked about (1) the size of their elderly population, (2) general information about dental education; (3) the number of dental schools teaching geriatric dentistry, and their teaching methods; (4) advanced training in geriatric dentistry; (5) scholarship/research in geriatric dentistry. RESULTS AND CONCLUSION: (1) There is great variation in the size of elderly population; (2) duration of training and content of dental education curriculum varies; (3) geriatric dentistry has not been established as a standalone course in dental schools in the majority of the countries, (4) most countries, with the exception of Japan, lack adequate number of dentists trained in geriatric dentistry as well as training programs, and (5) geriatric dentistry-related research has increased in recent years in scope and content, although the majority of these papers are not in English.

Emerging Diagnostic and Therapeutic Potentials of Human Hair Proteomics.

The use of noninvasive human substrates to interrogate pathophysiological conditions has become essential in the post- Human Genome Project era. Due to its high turnover rate, and its long term capability to incorporate exogenous and endogenous substances from the circulation, hair testing is emerging as a key player in monitoring long term drug compliance, chronic alcohol abuse, forensic toxicology, and biomarker discovery, among other things. Novel high-throughput 'omics based approaches like proteomics have been underutilized globally in comprehending human hair morphology and its evolving use as a diagnostic testing substrate in the era of precision medicine. There is paucity of scientific evidence that evaluates the difference in drug incorporation into hair based on lipid content, and very few studies have addressed hair growth rates, hair forms, and the biological consequences of hair grooming or bleaching. It is apparent that protein-based identification using the human hair proteome would play a major role in understanding these parameters akin to DNA single nucleotide polymorphism profiling, up to single amino acid polymorphism resolution. Hence, this work seeks to identify and discuss the progress made thus far in the field of molecular hair testing using proteomic approaches, and identify ways in which proteomics would improve the field of hair research, considering that the human hair is mostly composed of proteins. Gaps in hair proteomics research are identified and the potential of hair proteomics in establishing a historic medical repository of normal and disease-specific proteome is also discussed.

Omics-based molecular techniques in oral pathology centred cancer: prospect and challenges in Africa.

BACKGROUND: The completion of the human genome project and the accomplished milestones in the human proteome project; as well as the progress made so far in computational bioinformatics and "big data" processing have contributed immensely to individualized/personalized medicine in the developed world. MAIN BODY: At the dawn of precision medicine, various omics-based therapies and bioengineering can now be applied accurately for the diagnosis, prognosis, treatment, and risk stratification of cancer in a manner that was hitherto not thought possible. The widespread introduction of genomics and other omics-based approaches into the postgraduate training curriculum of diverse medical and dental specialties, including pathology has improved the proficiency of practitioners in the use of novel molecular signatures in patient management. In addition, intricate details about disease disparity among different human populations are beginning to emerge. This would facilitate the use of tailor-made novel theranostic methods based on emerging molecular evidences. CONCLUSION: In this review, we examined the challenges and prospects of using currently available omics-based technologies vis-à-vis oral pathology as well as prompt cancer diagnosis and treatment in a resource limited setting.

Emerging proteomics biomarkers and prostate cancer burden in Africa.

Various biomarkers have emerged via high throughput omics-based approaches for use in diagnosis, treatment, and monitoring of prostate cancer. Many of these have yet to be demonstrated as having value in routine clinical practice. Moreover, there is a dearth of information on validation of these emerging prostate biomarkers within African cohorts, despite the huge burden and aggressiveness of prostate cancer in men of African descent. This review focusses of the global landmark achievements in prostate cancer proteomics biomarker discovery and the potential for clinical implementation of these biomarkers in Africa. Biomarker validation processes at the preclinical, translational and clinical research level are discussed here, as are the challenges and prospects for the evaluation and use of novel proteomic prostate cancer biomarkers.

Seminal Fluid-Mediated Inflammation in Physiology and Pathology of the Female Reproductive Tract.

Inflammation is a multifaceted process involving a host of resident and recruited immune cells that eliminate the insult or injury and initiate tissue repair. In the female reproductive tract (FMRT), inflammation-mediated alterations in epithelial, vascular, and immune functions are important components of complex physiological processes and many local and systemic pathologies. It is well established that intracoital and postcoital function of seminal fluid (SF) goes beyond nutritive support for the spermatozoa cells. SF, in particular, the inflammatory bioactive lipids, and prostaglandins present in vast quantities in SF, have a role in localized immune modulation and regulation of pathways that can exacerbate inflammation in the FMRT. In sexually active women SF-mediated inflammation has been implicated in physiologic processes such as ovulation, implantation, and parturition while also enhancing tumorigenesis and susceptibility to infection. This review highlights the molecular mechanism by which SF regulates inflammatory pathways in the FMRT and how alterations in these pathways contribute to physiology and pathology of the female reproductive function. In addition, based on findings from TaqMan® 96-Well Plate Arrays, on neoplastic cervical cells treated with SF, we discuss new findings on the role of SF as a potent driver of inflammatory and tumorigenic pathways in the cervix.

Novel potential serological prostate cancer biomarkers using CT100+ cancer antigen microarray platform in a multi-cultural South African cohort.

There is a growing need for high throughput diagnostic tools for early diagnosis and treatment monitoring of prostate cancer (PCa) in Africa. The role of cancer-testis antigens (CTAs) in PCa in men of African descent is poorly researched. Hence, we aimed to elucidate the role of 123 Tumour Associated Antigens (TAAs) using antigen microarray platform in blood samples (N = 67) from a South African PCa, Benign prostatic hyperplasia (BPH) and disease control (DC) cohort. Linear (fold-over-cutoff) and differential expression quantitation of autoantibody signal intensities were performed. Molecular signatures of candidate PCa antigen biomarkers were identified and analyzed for ethnic group variation. Potential cancer diagnostic and immunotherapeutic inferences were drawn. We identified a total of 41 potential diagnostic/therapeutic antigen biomarkers for PCa. By linear quantitation, four antigens, GAGE1, ROPN1, SPANXA1 and PRKCZ were found to have higher autoantibody titres in PCa serum as compared with BPH where MAGEB1 and PRKCZ were highly expressed. Also, p53 S15A and p53 S46A were found highly expressed in the disease control group. Statistical analysis by differential expression revealed twenty-four antigens as upregulated in PCa samples, while 11 were downregulated in comparison to BPH and DC (FDR = 0.01). FGFR2, COL6A1and CALM1 were verifiable biomarkers of PCa analysis using urinary shotgun proteomics. Functional pathway annotation of identified biomarkers revealed similar enrichment both at genomic and proteomic level and ethnic variations were observed. Cancer antigen arrays are emerging useful in potential diagnostic and immunotherapeutic antigen biomarker discovery.

In silico verification and parallel reaction monitoring prevalidation of potential prostate cancer biomarkers.

PURPOSE: Targeted proteomics of potential biomarkers is often challenging. Hence, we developed an intermediate workflow to streamline potential urinary biomarkers of prostate cancer (PCa). MATERIALS & METHODS: Using previously discovered potential PCa biomarkers; we selected proteotypic peptides for targeted validation. Preliminary in silico immunohistochemical and single reaction monitoring (SRM) verification was performed. Successful PTPs were then prevalidated using parallel reaction monitoring (PRM) and reconfirmed in 15 publicly available databases. RESULTS: Stringency-based targetable potential biomarkers were shortlisted following in silico screening. PRM reveals top 12 potential biomarkers including the top ranking seven in silico verification-based biomarkers. Database reconfirmation showed differential expression between PCa and benign/normal prostatic urine samples. CONCLUSION: The pragmatic penultimate screening step, described herein, would immensely improve targeted proteomics validation of potential disease biomarkers.

Discovery of novel candidate urinary protein biomarkers for prostate cancer in a multiethnic cohort of South African patients via label-free mass spectrometry.

PURPOSE: Improvement in diagnostic accuracy of prostate cancer (PCa) progression using MS-based methods to analyze biomarkers in our African, Caucasian, and Mixed Ancestry patients can advance early detection and treatment monitoring. EXPERIMENTAL DESIGN: MS-based proteomic analysis of pooled (N = 36) and individual samples (N = 45) of PCa, benign prostatic hyperplasia, normal healthy controls, and patients with other uropathies was used to identify differences in proteomics profile. Samples were analyzed for potential biomarkers and proteome coverage in African, Caucasian, and Mixed Ancestry PCa patients. RESULTS: A total of 1102 and 5595 protein groups and nonredundant peptides, respectively, were identified in the pooling experiments (FDR = 0.01). Twenty potential biomarkers in PCa were identified and fold differences ± 2SD were observed in 17 proteins using intensity-based absolute quantification. Analysis of 45 individual samples yielded 1545 and 9991 protein groups and nonredundant peptides, respectively. Seventy-three (73) proteins groups, including existing putative PCa biomarkers, were found to be potential biomarkers of PCa by label-free quantification and demonstrated ethnic trends within our PCa cohort. CONCLUSION AND CLINICAL RELEVANCE: Urinary proteomics is a promising route to PCa biomarker discovery and may serve as source of ethnic-related biomarkers of PCa.