Transcriptomic profiling and genomic rearrangement landscape of Nigerian prostate cancer.

BACKGROUND: Men of African ancestry have disproportionately high incidence rates of prostate cancer (PCa) and have high mortality rates. While there is evidence for a higher genetic predisposition for incidence of PCa in men of African ancestry compared to men of European ancestry, there have been few transcriptomic studies on PCa in men of African ancestry in the African continent. OBJECTIVE: We performed transcriptomic profiling and fusion analysis on bulk RNA sequencing (RNA-seq) samples from 24 Nigerian PCa patients to investigate the transcriptomic and genomic rearrangement landscape of PCa in Nigerian men. DESIGN: Bulk RNA-seq was performed on 24 formalin-fixed paraffin-embeded (FFPE) prostatectomy specimens of Nigerian men. Transcriptomic analysis was performed on 11 high-quality samples. Arriba Fusion and STAR Fusion were used for fusion detection. RESULTS: 4/11 (36%) of the samples harbored an erythroblast transformation-specific (ETS) fusion event; 1/11 (9%) had a TMPRSS2-ERG fusion; 2/11 had a TMPRSS2-ETV5 fusion, and 1/11 had a SLC45A3-SKIL fusion. Hierarchical clustering of normalized and mean-centered gene expression showed clustering of fusion positive samples. Furthermore, we developed gene set signatures for Nigerian PCa based on fusion events. By projecting the cancer genome atlas prostate adenocarcinoma (TCGA-PRAD) bulk RNA-seq data set onto the transcriptional space defined by these signatures derived from Nigerian PCa patients, we identified a positive correlation between the Nigerian fusion signature and fusion positive samples in the TCGA-PRAD data set. CONCLUSIONS: Less frequent ETS fusion events other than TMPRSS2-ERG such as TMPRSS2-ETV5 and non-ETS fusion events such as SLC45A3-SKIL may be more common in PCa in Nigerian men. This study provides useful working transcriptomic signatures that characterize oncogenic states representative of specific gene fusion events in PCa from Nigerian men.

Potential epigenetic modifications implicated in triple- to quadruple-negative breast cancer transition: a review.

Current research on triple-negative breast cancer (TNBC) has resulted in delineation into the quadruple-negative breast cancer (QNBC) subgroup. Epigenetic modifications such as DNA methylation, histone posttranslational modifications and associated changes in chromatin architecture have been implicated in breast cancer pathogenesis. Herein, the authors highlight genes with observed epigenetic modifications that are associated with more aggressive TNBC/QNBC pathogenesis and possible interventions. Advanced literature searches were done on PubMed/MEDLINE, Scopus and Google Scholar. The results suggest that nine epigenetically altered genes/differentially expressed proteins in addition to the downregulated androgen receptor are associated with TNBC aggressiveness and could be implicated in the TNBC to QNBC transition. Thus, restoring the normal expression of these genes via epigenetic reprogramming could be therapeutically beneficial to TNBC and QNBC patients.

When the androgen hormone receptor becomes inactive in triple-negative breast cancer (TNBC) patients, it results in another subtype of breast cancer called quadruple-negative breast cancer (QNBC). This is because these patients already lack the biological activities of three other important hormone receptors. The functions of these receptors are targeted by some drugs used in the management of breast cancers, so the lack of these receptors in TNBC and QNBC patients is thought to be linked with poor response to treatment. Some epigenetic modifications are involved in a more severe disease that is very difficult to control in TNBC patients and could facilitate its transition to the more aggressive QNBC subtype. Treatment response could be improved by restoring the normal function of the altered genes by reversing the observed epigenetic alterations.

Epidemiology of SARS-CoV2 in Qatar's primary care population aged 10 years and above.

BACKGROUND: There is an urgent need to elucidate the epidemiology of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and characterize its potential impact. Investing in characterising the SARS-CoV2 will help plan and improve the response to the pandemic. Furthermore, it will help identify the most efficient ways of managing the pandemic, avoiding public health policies and interventions that may be unduly restrictive of normal activity or unnecessarily costly. This paper describes the design and reports findings of a population based epidemiological study undertaken to characterise SARS-CoV2 in Qatar using limited resources in a timely manner. METHODS: Asymptomatic individuals ≥10 years registered with Qatar's publicly funded primary health provider were eligible. A stratified random sampling technique was utilized to identify the study sample. Participants were invited to an appointment where they completed a questionnaire and provided samples for polymerase chain reaction and Immunoglobulin M and G immunoassay tests. Data collected were analyzed to calculate point and period prevalence by sociodemographic, lifestyle and clinical characteristics. RESULTS: Of 18,918 individuals invited for the study, 2084 participated (response rate 10.8%). The overall point prevalence and period prevalence were estimated to be 1.6% (95% CI 1.1-2.2) and 14.6% (95% CI 13.1-16.2) respectively. Period prevalence of SARS-CoV2 infection was not considerably different across age groups (9.7-19.8%). It was higher in males compared to females (16.2 and 12.7% respectively). A significant variation was observed by nationality (7.1 to 22.2%) and municipalities (6.9-35.3%). CONCLUSIONS: The study provides an example of a methodologically robust approach that can be undertaken in a timely manner with limited resources. It reports much-needed epidemiological data about the spread of SARS-CoV2. Given the low prevalence rates, majority of the population in Qatar remains susceptible. Enhanced surveillance must continue to be in place, particularly due to the large number of asymptomatic cases observed. Robust contact tracing and social distancing measures are key to prevent future outbreaks.

Prognostic significance of BIRC7/Livin, Bcl-2, p53, Annexin V, PD-L1, DARC, MSH2 and PMS2 in colorectal cancer treated with FOLFOX chemotherapy with or without aspirin.

Evasion of apoptosis is associated with treatment resistance and metastasis in colorectal cancer (CRC). Various cellular processes are associated with evasion of apoptosis. These include overexpression of pro-apoptotic proteins (including p53 and PD-L1), anti-apoptotic proteins (BIRC7/Livin and Bcl-2), chemokine receptors (including DARC), and dysregulation of DNA mismatch repair proteins (including MSH2 and PMS2). The aim of this study was to determine the effect of folinic acid, 5-FU and oxaliplatin (FOLFOX) as a single agent and aspirin plus FOLFOX in various combinations on the aforementioned proteins in human CRC, SW480 cell line and rat models of N-Methyl-N-Nitrosourea (NMU)-induced CRC. In addition, effects of the NMU-induced CRC and chemotherapeutic regimens on haematological and biochemical parameters in the rat models were studied. Immunohistochemistry, immunofluorescence and immunoblot techniques were used to study the expression pattern of the related proteins in the human CRC cells pre- and post-treatment. Double contrast barium enema, post-mortem examination and histological analyses were used to confirm tumour growth and the effect of the treatment in vivo in rat models. Notably, we found in human mucinous CRC, a significant increase in expression of the BIRC7/Livin post-FOLFOX treatment compared with pre-treatment (p = 0.0001). This increase provides new insights into the prognostic role of BIRC7/Livin in evasion of apoptosis and facilitation of treatment resistance, local recurrence and metastasis particularly among mucinous CRCs post-FOLFOX chemotherapy. These poor prognostic features in the CRC may be further compounded by the significant suppression of DARC, PD-L1, PMS2 and overexpression of MSH2 and anti-apoptotic Bcl-2 and p53 proteins observed in our study (p < 0.05). Importantly, we found a significant reduction in expression of BIRC7/Livin and reactivation of DARC and PD-L1 with a surge in Annexin V expression in rat models of CRC cells post-treatment with a sequential dose of aspirin plus FOLFOX compared with other treatments in vivo (p <0.05). The mechanistic rational of these effects underscores the importance of expanded concept of possible aspirin combination therapy with FOLFOX sequentially in future CRC management. Validation of our findings through randomized clinical trials of aspirin plus FOLFOX sequentially in patients with CRC is therefore warranted.

Patterns of Early-Onset Colorectal Cancer Among Nigerians and African Americans.

PURPOSE: Colorectal cancer (CRC) incidence rates are increasing among individuals < 50 years of age (early-onset CRC) globally with causes unknown. Racial/ethnic disparities in early-onset CRC have also grown more pronounced, because Black individuals have higher early-onset CRC incidence and poorer survival compared with White individuals. We describe the prevalence and burden of early-onset CRC among Africans in Nigeria and African Americans (AAs) in the United States. PATIENTS AND METHODS: We identified Black individuals diagnosed with a first primary CRC ages 18 to 49 years between 1989 and 2017 at Ahmadu Bello University Teaching Hospital in Zaria, Nigeria (Nigerians), and in the United States (AAs) using the National Institutes of Health/National Cancer Institute's SEER program of cancer registries. Multivariable logistic regression models were used to investigate clinical and demographic differences between Nigerians and AAs with early-onset CRC, adjusted for age, sex, tumor site, and histology. RESULTS: A total of 5,019 Black individuals were diagnosed with early-onset CRC over the study period (379 Nigerians; 4,640 AAs). Overall, approximately one third of young Black patients were diagnosed with rectal tumors (35.8%). Nigerian individuals with early-onset CRC were eight-fold more likely to be diagnosed with rectal tumors (odds ratio [OR], 8.14; 95% CI, 6.23 to 10.62; P < .0001) and more likely to be diagnosed at younger ages (OR, 0.87; 95% CI, 0.86 to 0.89; P < .0001) compared with young African Americans in adjusted models. CONCLUSION: Compared with AA individuals diagnosed with early-onset CRC, Nigerian individuals harbor distinct features of early-onset CRC. Additional investigation of the histopathologic and biologic heterogeneity of early-onset CRCs among Black individuals is critical for understanding racial disparities in susceptibility and outcomes, which may have implications for tailored early-onset CRC prevention, detection, and treatment strategies.

An analysis of dietary fiber and fecal fiber components including pH in rural Africans with colorectal cancer.

BACKGROUND/AIMS: Colorectal cancer (CRC) is now a major public health problem with heavy morbidity and mortality in rural Africans despite the lingering dietary fiber-rich foodstuffs consumption. Studies have shown that increased intake of dietary fiber which contribute to low fecal pH and also influences the activity of intestinal microbiota, is associated with a lowered risk for CRC. However, whether or not the apparent high dietary fiber consumption by Africans do not longer protects against CRC risk is unknown. This study evaluated dietary fiber intake, fecal fiber components and pH levels in CRC patients. METHODS: Thirty-five subjects (CRC=21, control=14), mean age 45 years were recruited for the study. A truncated food frequency questionnaire and modified Goering and Van Soest procedures were used. RESULTS: We found that all subjects consumed variety of dietary fiber-rich foodstuffs. There is slight preponderance in consumption of dietary fiber by the control group than the CRC patients. We also found a significant difference in the mean fecal neutral detergent fiber, acid detergent fiber, hemicellulose, cellulose and lignin contents from the CRC patients compared to the controls (P<0.05). The CRC patients had significantly more fecal pH level than the matched apparently healthy controls (P=0.017). CONCLUSIONS: The identified differences in the fecal fiber components and stool pH levels between the 2 groups may relate to CRC incidence and mortality in rural Africans. There is crucial need for more hypothesis-driven research with adequate funding on the cumulative preventive role of dietary fiber-rich foodstuffs against colorectal cancer in rural Africans "today."