Salivary creatinine as a diagnostic tool for evaluating patients with chronic kidney disease

Magister Scientiae Dentium - MSc(Dent)BACKGROUND Preliminary studies have shown the potential use of saliva in the diagnosis of chronic kidney disease (CKD). For saliva to completely replace serum as a diagnostic and monitoring tool for CKD, studies must be done to determine its effectiveness as a substitute in diagnosing chronic kidney disease, at each stage of the disease. Aim: The aim of the study was to evaluate the role of saliva as a safe and non-invasive alternative to serum, for creatinine estimation, in all stages of chronic kidney disease. METHOD A cross sectional study was conducted at the Renal Unit of Tygerberg Hospital, on 230 patients at all stages of CKD. Informed consent was obtained; thereafter saliva and serum samples were collected for creatinine analysis. Correlation between serum and salivary creatinine was determined using Spearman's correlation test. Receiver Operating Characteristics (ROC) analysis was used to determine the diagnostic ability of salivary creatinine and a cut-off value for sensitivity and specificity of salivary creatinine to diagnose CKD with GFR < 60ml/min was obtained. RESULTS Serum creatinine values ranged from 46?mol/L to 1581?mol/L with a median value of 134?mol/L. Salivary creatinine values ranged from 3?mol/L to 400?mol/L with a median of 11?mol/L. Spearman's correlation analysis showed a strong positive correlation (r = 0.82) between serum and salivary creatinine values for all CKD stages. Linear regression analysis of serum and salivary creatinine for CKD patients was significant in all CKD stages, except for stage 1. Area under the curve for salivary creatinine was 0.839. A cut-off value of 8.50?mol/L showed a sensitivity of 78.3% and specificity of 74.0% at eGFR < 60ml/min, for classifying patients as having CKD

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

Potential of miRNAs in Plasma Extracellular Vesicle for the Stratification of Prostate Cancer in a South African Population

Prostate cancer (PCa) is the most common cause of cancer death among African men. The analysis of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) can be utilized as a non-invasive tool for the diagnosis of PCa. In this study, we used small RNA sequencing to profile miRNAs cargo in plasma EVs from South African PCa patients. We evaluated the differential expression of miRNAs between low and high Gleason scores in the plasma EVs of South African patients and in the prostatic tissue from data available in the Cancer Genome Atlas (TCGA) Data Portal. We identified 7 miRNAs differently expressed in both EVs and prostatic tissues. We evaluated their expression using qPCR in a larger cohort of 10 patients with benign prostatic hyperplasia (BPH) and 24 patients with PCa. Here, we reported that the ratio between two of these miRNAs (i.e., miR-194-5p/miR-16-5p) showed a higher concentration in PCa compared to BPH and in metastatic PCa compared to localized PCa. We explored for the first time the profiling of miRNAs cargo in plasma EVs as a tool for the identification of putative markers in the South African population. Our finding indicated the ratio miR-194-5p/miR-16-5p as a non-invasive marker for the evaluation of PCa aggressiveness in this population

Detection of Cancer-Associated Gene Mutations in Urinary Cell-Free DNA among Prostate Cancer Patients in South Africa

Prostate cancer (PCa) is the most common cause of cancer death among African men. The presence of tumor-specific variations in cell-free DNA (cfDNA), such as mutations, microsatellite instability, and DNA methylation, has been explored as a source of biomarkers for cancer diagnosis. In this study, we investigated the diagnostic role of cfDNA among South African PCa patients. We performed whole exome sequencing (WES) of urinary cfDNA. We identified a novel panel of 31 significantly deregulated somatic mutated genes between PCa and benign prostatic hyperplasia (BPH). Additionally, we performed whole-genome sequencing (WGS) on matching PCa and normal prostate tissue in an independent PCa cohort from South Africa. Our results suggest that the mutations are of germline origin as they were also found in the normal prostate tissue. In conclusion, our study contributes to the knowledge of cfDNA as a biomarker for diagnosing PCa in the South African population

Liquid Biopsy in Head and Neck Cancer: Its Present State and Future Role in Africa

The rising mortality and morbidity rate of head and neck cancer (HNC) in Africa has been attributed to factors such as the poor state of health infrastructures, genetics, and late presentation resulting in the delayed diagnosis of these tumors. If well harnessed, emerging molecular and omics diagnostic technologies such as liquid biopsy can potentially play a major role in optimizing the management of HNC in Africa. However, to successfully apply liquid biopsy technology in the management of HNC in Africa, factors such as genetic, socioeconomic, environmental, and cultural acceptability of the technology must be given due consideration. This review outlines the role of circulating molecules such as tumor cells, tumor DNA, tumor RNA, proteins, and exosomes, in liquid biopsy technology for the management of HNC with a focus on studies conducted in Africa. The present state and the potential opportunities for the future use of liquid biopsy technology in the effective management of HNC in resource-limited settings such as Africa is further discussed

Developmental defects of the enamel and its impact on the oral health quality of life of children resident in Southwest Nigeria

Abstract Background Developmental defects of the enamel (DDE) increase the risk for diseases that impact negatively on the quality of life. The objective of this study was to compare the oral health quality of life of children with molar-incisor-hypomineralisation (MIH) and enamel hypoplasia; and assess if caries worsened the impact of these lesions on the quality of life. Methods This study recruited 853 6 to 16-years-old school children. They filled the Child-OIDP questionnaire. The MIH, enamel hypoplasia, caries and oral hygiene status was assessed. Poisson regression was used to determine the impact of MIH and enamel hypoplasia on the oral health quality of life, after adjusting for the effect of sex, age, socioeconomic class, oral hygiene and caries status. Results The prevalence of MIH and enamel hypoplasia was 2.9% and 7.6% respectively. There was no significant difference in the mean child-OIDP scores of children with or without MIH (p = 0.57), children with or without enamel hypoplasia (p = 0.48), and children with enamel hypoplasia with and without caries (p = 0.30). Children with enamel hypoplasia and caries had worse outcomes for speaking (p = 0.01). Children with middle (AOR: 2.74; 95% CI: 1.60–4.67; P < 0.01) and low (AOR: 1.75; 95% CI: 1.04–2.95; p = 0.03) socioeconomic status, and those with caries (AOR: 2.02; 95% CI: 1.26–3.22; p = 0.03) had their oral health quality of life negatively impacted. Conclusion MIH and enamel hypoplasia had no significant impact on the overall oral health quality of life of children resident in southwestern Nigeria. However, children with caries and those from middle and low socioeconomic classes had poorer oral health quality of life

Detection of Cancer-Associated Gene Mutations in Urinary Cell-Free DNA among Prostate Cancer Patients in South Africa

Prostate cancer (PCa) is the most common cause of cancer death among African men. The presence of tumor-specific variations in cell-free DNA (cfDNA), such as mutations, microsatellite instability, and DNA methylation, has been explored as a source of biomarkers for cancer diagnosis. In this study, we investigated the diagnostic role of cfDNA among South African PCa patients. We performed whole exome sequencing (WES) of urinary cfDNA. We identified a novel panel of 31 significantly deregulated somatic mutated genes between PCa and benign prostatic hyperplasia (BPH). Additionally, we performed whole-genome sequencing (WGS) on matching PCa and normal prostate tissue in an independent PCa cohort from South Africa. Our results suggest that the mutations are of germline origin as they were also found in the normal prostate tissue. In conclusion, our study contributes to the knowledge of cfDNA as a biomarker for diagnosing PCa in the South African population

The prospect and challenges to the flow of liquid biopsy in Africa

Liquid biopsy technologies have the potential to transform cancer patient management as it others non- invasive diagnosis and real-time monitoring of disease progression and treatment responses. The use of liquid biopsy for non-invasive cancer diagnosis can have pivotal importance for the African continent where access to medical infrastructures is limited, as it eliminates the need for surgical biopsies. To apply liquid biopsy technologies in the African setting, the influence of environmental and population genetic factors must be known. In this review, we discuss the use of circulating tumor cells, cell-free nucleic acids, extracellular vesicles, protein, and other biomolecules in liquid biopsy technology for cancer management with special focus on African studies. We discussed the prospect, barriers, and other aspects that pose challenges to the use of liquid biopsy in the African continent