Novel urinary and serological markers of prostate cancer using proteomics techniques: an important tool for early cancer diagnosis and treatment monitoring

In Africa, Prostate cancer (PCa) is the most frequently diagnosed solid organ tumour in males and use of prostate specific antigen (PSA) is presently fraught with diagnostic inaccuracies. Not least, in a multi-ethnic society like South Africa, proteome differences between African, Caucasian and Mixed-Ancestry PCa patients are largely unknown. Hence, discovery and validation of affordable, non-invasive and reliable diagnostic biomarkers of PCa would expand the frontiers of PCa management. We have employed two high-throughput proteomics technologies to identify novel urine- and blood-based biomarkers for early diagnosis and treatment monitoring of prostate cancer in a South African cohort as well as elucidate proteome differences in patients from our heterogeneous cohort. We compared the urinary proteomes of PCa, Benign Prostatic Hyperplasia (BPH), disease controls comprising patients with other uropathies (DC) and normal healthy controls (NC) both by pooling and individual discovery shotgun proteomic assessment on a nano-Liquid chromatography (nLC) coupled Hybrid Quadrupole-Orbitrap Mass Spectrometer platform. In-silico verification of identified biomarkers was performed using the Human Protein Atlas (HPA) as well as SRMAtlas; and verified potential biomarkers were experimentally prevalidated using a targeted parallel reaction monitoring (PRM) proteomics approach. Further, we employed the CT100+ antigen microarray platform to assess the differential humoral antibody response of PCa, DC and BPH patients in our cohort to a panel of 123 tumour-associated cancer antigens. Candidate antigen biomarkers were analyzed for ethnic group variation in our cohort and potential cancer diagnostic and immunotherapeutic inferences were drawn. Using these approaches, we identified 5595 and 9991 non-redundant peptides from the pooled and individual experiments respectively. While nine proteins demonstrated ethnic trend, 37 and 73 proteins were differentially expressed by pooled and individual analysis respectively. All 32 verified biomarkers were prevalidated with parallel reaction monitoring. Good PRM signals for 12 top ranking biomarker was observed, including PSA and prostatic acid phosphatase. We also identified 41 potential diagnostic and immunotherapeutic antigen biomarkers. Proteogenomic functional pathway analyses of differentially expressed antigens showed similar enrichments of biologic processes. We identified herein novel urinary and blood-based potential diagnostic biomarkers and immunotherapeutic targets of PCa in a South African PCa Cohort using multiple proteomics approaches

Potential latitudinal variation in orodigestive tract cancers in Africa

BACKGROUND. Previous studies have alluded to a causal relationship between pathological entities and geographical variations, but there is a paucity of studies from Africa discussing the effect of latitudinal variation on orodigestive cancers in this region. It seems plausible that the burden of orodigestive cancer would differ as a result of variations in diet, cultural habits, climate and environmental conditions down the length of Africa. OBJECTIVES. To analyse regional variations in prevalence, incidence and mortality data in the global cancer statistics database (GLOBOCAN 2012) curated by the World Health Organization and the International Agency for Research on Cancer. Basic descriptive statistical tools were used to depict regional variations in cancer morbidity and mortality. METHODS. Data on 13 African countries between longitude 20⁰ and 30⁰ east and latitude 35⁰ north and 35⁰ south were examined for variation in age-standardised orodigestive cancer prevalence, incidence and mortality. Possible regional causes for orodigestive tract cancer development were investigated. Data on lip and oral cavity, oesophageal, gastric, colorectal, liver, gallbladder and pancreatic cancers in the RESULTS. Our empirical findings from this preliminary study support the notion that the incidence and prevalence of orodigestive cancers vary within Africa. This effect may be due to environmental, economic, political and possibly genetic factors. CONCLUSIONS. Considering the heterogeneity of the above factors across Africa, disbursement of funding for cancer research and therapy in Africa should be focused in terms of regional variations to make best use of the fiscal allocation by African governments, non-governmental organisations and international agencies

The physician-scientists: rare species in Africa

There is paucity of physician-scientists in Africa, resulting in overt dependence of clinical practice on research findings from advanced "first world" countries. Physician-scientists include individuals with a medical degree alone or combined with other advanced degrees (e.g. MD/MBChB and PhD) with a career path in biomedical/ translational and patient-oriented/evaluative science research. The paucity of clinically trained research scientists in Africa could result in dire consequences as exemplified in the recent Ebola virus epidemic in West Africa, where shortage of skilled clinical scientists, played a major role in disease progression and mortality. Here we contextualise the role of physician-scientist in health care management, highlight factors limiting the training of physician-scientist in Africa and proffer implementable recommendations to address these factors

The COVID-19 pandemic: the benefits and challenges it presents for medical education in Africa

The coronavirus disease (COVID-19) has impacted many facets of everyday daily life, resulting in far-reaching consequences on social interaction, regional and global economies, and healthcare delivery systems. Numerous reports have commented on the impact of the COVID-19 pandemic on medical education in various world regions. However, we know little about the influence of the pandemic on medical education in Africa. Here, we discuss the potential impact of COVID-19 on teaching and learning in undergraduate medical education in sub-Saharan Africa, illustrating some of the unexpected benefits and challenges the pandemic presents for medical education in sub-Saharan Africa

Medical education units: A necessity for quality assurance in health professions education in Nigeria

In recent years, curricula and pedagogical methods in medical education have undergone rapid and unprecedented changes globally. The emphasis has shifted from traditional, teacher-centred learning, characterised by the accumulation of non-integrated volumes of knowledge, to active, student-centred learning. The Medical and Dental Council of Nigeria (MDCN) reports that there are 31 fully accredited and 6 partially accredited medical schools in Nigeria. The majority of these medical schools still offer undergraduate medical training based on a curriculum characterised by a distinct separation of preclinical and clinical training, with minimal or no integration. This approach is coupled with low-quality teaching by medical educators, as many medical colleges in Nigeria presently use specialists as lecturers who have little or no training in higher education practices; their only exposure to teaching is that obtained during their postgraduate specialty training. Similarly, very few medical schools in Nigeria have established medical education units (MEUs), as recommended by the World Health Organization and the World Federation for Medical Education. We discuss the shortcomings of the present medical education system in Nigeria and suggest ways to improve the quality of pedagogy among Nigerian medical educators, such as the establishment of clinical-skills centres and MEUs at Nigerian medical schools. In addition, this review highlights the role and importance of MEUs in facilitating quality assurance in health professions education, and the urgent need for more medical schools in Nigeria to establish MEUs to promote, co-ordinate and evaluate medical education reforms based on needs assessments and within the confines of MDCN standards

Diagnostic Potential of Salivary Exosomes in Oral Cancer

“Omics” based concepts and techniques are gaining momentum in the field of oral medicine, spurred on by rapid advancements within the field of precision diagnostics and therapeutics. Oral cancer, specifically oral squamous cell carcinoma is the most common head and neck cancer, posing both diagnostic and prognostic challenges globally. Saliva offers several advantages as a diagnostic tool and has gained recognition as a biological medium for liquid biopsy. Salivary biomarkers, such as exosomes not only contain the full spectrum of genomic, lipidomic and proteomic material from its cell of origin, but are also more stable and consistently measurable in saliva due to their phospholipid structural protection of their merchandise/contents. Salivary exosomes are mediators in communication and transfer of contents between cancer and normal cells and thus key role players in mediating the tumor environment. Even though exosomes have been widely employed to investigate systemic diseases including head and neck cancers, unraveling the biologic mechanisms, scope of application of salivary tumor-derived exosomes and overcoming restrictions in this emergent field of saliva-exosomics warrants further investigation

Human Hair as a Testing Substrate in the Era of Precision Medicine: Potential Role of ‘Omics-Based Approaches

Minimally and noninvasive investigation of pathology and treatment monitoring is highly attractive in medicine. The use of human hair samples as a non-invasive testing substrate is potentially poised to improve diagnostic and forensic medicine. Hair has the unique ability to capture long-term information about health and disease in an individual as compared to urine and blood. Testing long hair offers a potential means of long-term monitoring of drug compliance, drug abuse, chronic alcohol abuse, and diagnostic biomarker discovery. Even though human hair is mostly composed of keratin and keratin-associated proteins, very little literature has been published on human hair proteomics. Emerging high throughput omics based techniques such as proteomics are increasingly improving our depth of knowledge about the diagnosis, prognosis and prediction of diseases globally. Although many aspects of the use of these novel molecular aids to improve disease diagnosis and patient management remains elusive; it is evident that these techniques have improved precision medicine tremendously. This chapter aims to discuss current plausible application of human hair omics-based approaches to the field of pathology, diagnostics and precision/individualized medicine

Ameloblastic carcinoma: a clinicopathologic analysis of cases seen in a Nigerian Teaching Hospital and review of literature

Introduction: ameloblastic carcinoma is a rare malignant odontogenic neoplasm that exhibits histological features of ameloblastoma in combination with cytological atypia. It may arise de novo or secondarily through malignant de-differentiation of pre-existing ameloblastoma or odontogenic cyst. Secondary ameloblastic carcinomas often results from repeated surgical intervention, which is a mainstay of odontogenic tumor management in resource limited settings. To date, relatively few cases of ameloblastic carcinomas have been reported and many cases have been misdiagnosed as ameloblastoma. This is due to its wide range of clinicopathological feature which range from indolent to aggressive. It may present as an aggressive ulcerated mass or as a simple cystic lesion; hence, it often challenging to delineate from its benign counterpart, ameloblastoma. Methods: this study reviewed the clinicopathological data on 157 cases of odontogenic tumors diagnosed over a 10 years period from the pathology archive of the Oral Pathology Unit of Obafemi Awolowo University Teaching Hospital Complex (OAUTHC), Ile-Ife, Nigeria. Results: of all these cases, we identified that 64.9% were Ameloblastomas, while 8.3% were ameloblastic carcinomas. Primary subtypes of ameloblastic carcinoma constituted 23.08%, while 69.23% of the cases were of the secondary subtype. We also found that the secondary subtype of ameloblastic carcinomas showed a higher mean duration value of 7.7 years. Most lesions were found in posterior mandible and presented with ulceration, perforation and ill-defined borders radiographically. Conclusion: this study is among the few that have documented higher frequency of secondary ameloblastic carcinoma in the scientific literature

Targeted polymerase chain reaction-based expression of putative halitogenic bacteria and volatile sulphur compound analysis among halitosis patients at a tertiary hospital in Nigeria

Halitosis (bad breath) can be a cause of anxiety, depression and psychosocial stress, with pathological changes in the oral microbiota playing an important role in its development. Despite its prevalence, studies on the microbiology of halitosis are rare in Nigeria. This study determines the presence of five putative periodontal pathogens viz: Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola on the tongue dorsa of halitosis and non-halitosis patients using a 16S rDNA-directed polymerase chain reaction assay. Furthermore, an association of these bacteria with oral malodour [as assessed by volatile sulphur compounds (VSC) measurements] with a portable sulphide monitor, the Halimeter (Interscan Corp, Chatsworth, California), was performed

The practicality of the use of liquid biopsy in early diagnosis and treatment monitoring of oral cancer in resource- limited settings

An important driving force for precision and individualized medicine is the provision of tailor-made care for patients on an individual basis, in accordance with best evidence practice. Liquid biopsy(LB) has emerged as a critical tool for the early diagnosis of cancer and for treatment monitoring, but its clinical utility for oral squamous cell carcinoma (OSCC) requires more research and validation. Hence, in this review, we have discussed the current applications of LB and the practicality of its routine use in Africa; the potential advantages of LB over the conventional “gold-standard” of tissue biopsy; and finally, practical considerations were discussed in three parts: pre-analytic, analytic processing, and the statistical quality and postprocessing phases