Precision oncology can be defined as molecular profiling of tumors to identify targetable alterations. Emerging research reports the high mortality rates associated with type II endometrial cancer in black women and with prostate cancer in men of African ancestry. The lack of adequate genetic reference information from the African genome is one of the major obstacles in exploring the benefits of precision oncology in the African context. Whilst external factors such as the geography, environment, health-care access and socio-economic status may contribute greatly towards the disparities observed in type II endometrial and prostate cancers in black populations compared to Caucasians, the contribution of African ancestry to the contribution of genetics to the etiology of these cancers cannot be ignored. Non-coding RNAs (ncRNAs) continue to emerge as important regulators of gene expression and the key molecular pathways involved in tumorigenesis. Particular attention is focused on activated/repressed genes and associated pathways, while the redundant pathways (pathways that have the same outcome or activate the same downstream effectors) are often ignored. However, comprehensive evidence to understand the relationship between type II endometrial cancer, prostate cancer and African ancestry remains poorly understood. The sub-Saharan African (SSA) region has both the highest incidence and mortality of both type II endometrial and prostate cancers. Understanding how the entire transcriptomic landscape of these two reproductive cancers is regulated by ncRNAs in an African cohort may help elucidate the relationship between race and pathological disparities of these two diseases. This review focuses on global disparities in medicine, PCa and ECa. The role of precision oncology in PCa and ECa in the African population will also be discussed.
Prostate cancer (PCa) is a leading cause of mortality in men of African origin. While men of African descent in highincome countries (HICs) demonstrate poor prognosis compared to their European counterparts, African men on the African continent, particularly Southern Africa have shown even higher PCa mortality rates. Extrinsic factors such as the socioeconomic status, education level, income level, geographic location and race contribute to PCa patient outcome. These are further deepened by the African norms which are highly esteemed and may have detrimental effects on PCa patients' health. Insights into African cultures and social constructs have been identified as key elements towards improving men's health care seeking behaviour which will in turn improve PCa patients' outcome. Compared to Southern Africa, the Eastern, Western and Central African regions have lower PCa incidence rates but higher mortality rates. The availability of cancer medical equipment has also been reported to be disproportionate in Africa, with most cancer resources in Northern and Southern Africa. Even within Southern Africa, cancer management resources are unevenly available where one country must access PCa specialised care in the neighbouring countries. While PCa seems to be better managed in HICs, steps towards effective PCa management are urgently needed in Africa, as this continent represents a significant portion of lowmiddle-income countries (LMICs). Replacing African men in Africa with African American men may not optimally resolve PCa challenges in Africa. Adopting western PCa management practices can be optimised by integrating improved core-African norms. The aim of this review is to discuss PCa disparities in Africa, deliberate on the significance of integrating African norms around masculinity and discuss challenges and opportunities towards effective PCa care in Africa, particularly in Southern Africa.
Telomerase RNA component (TERC) is a long non-coding (lncRNA) associated with prostate cancer progression and has novel prognostic biomarker potential. Differential methylation patterns of lncRNAs affect their expression levels, leading to cancer. This study aimed to profile and elucidate differential lncRNA expression patterns in prostate cancer (PCa). A 384-well plate of PCa associated lncRNA gene array panel was used in castration resistant PC-3 PCa cells vs androgen-sensitive PCa LNCaP cells. Annotation and enrichment analysis of lncRNA differential gene expression was performed using a human lncRNA sets database, LncSEA. Furthermore, digital droplet PCR (ddPCR) was used to verify the PCR array results. Up or down-regulation of ±2 and p <0.05 were considered significant. Decreased hsa-miR-320 gene family expression has been reported in various tumors including PCa. However, the precise mechanisms of hsa-miR-320 gene family in PCa remain to be elucidated. Thirty six of 84 lncRNAs were shown to be upregulated, while 14% of the lncRNA genes were downregulated. Notably, TERC lncRNA was upregulated in high metastatic PC-3 cells. Hypermethylation patterns of this lncRNA in high metastatic PC-3 cells was also shown by enrichment analysis. Furthermore, TERC lncRNA was demonstrated to regulate the hsa-miR-320 family, suggesting a correlation between TERC hypermethylation and downregulation of hsa-miR-320 gene family expression in PCa, as revealed by bioinformatics analysis. TERC lncRNA promotes PCa cell proliferation, migration, invasion and metastasis by sponging hsa-miR-320 family. This TERC/hsa-miR-320 interaction holds potential to understanding PCa prognostic mechanisms by lncRNAs and may also be targeted for novel therapeutics. Citation Format: Mandisa Mbeje, Jeyalakshmi Kandhavelu, Clement Penny, Zodwa Dlamini, Rahaba Marima. Telomerase RNA component lncRNA regulates hsa-miR-320 family and promotes prostate cancer metastasis. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3785.
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