Subject(s)
Morale , Obstetricians , Obstetrics , Female , Humans , Obstetricians/psychology , Obstetrics/organization & administration , United KingdomABSTRACT
BACKGROUND: Current diagnostic tools are unable to distinguish low-grade indolent prostate cancer (PrCa) from that with a propensity to become metastatic and/or lethal. Recent evidence suggests that reprogramming of the transcriptome may drive the metastatic phenotype, and that this reprogramming is controlled, at least in part, by epigenetic changes to the DNA of cancer cells, including methylation. These changes, referred to as 'epigenetic drivers,' have previously been associated with cancer cell survival. METHODS: Here, using Illumina Methylation EPIC array data of paired primary PrCa and metastatic bone samples, we identified WNT5A as a putative epi-driver of PrCa metastasis to the bone, which was further validated in vitro. RESULTS: Significantly higher WNT5A methylation was observed in primary PrCa samples and 22Rv1 cells compared to metastatic bone samples and PC-3 cells. This higher methylation was associated with significantly lower WNT5A gene expression. CONCLUSION: Given the limited effective therapies available for metastatic cancer sufferers, particularly those whose disease has metastasised to the bone, WNT5A presents as a potential putative target for therapy.
Subject(s)
Bone Neoplasms , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Prostatic Neoplasms , Wnt-5a Protein , Humans , Wnt-5a Protein/metabolism , Wnt-5a Protein/genetics , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Bone Neoplasms/secondary , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Cell Line, Tumor , AgedSubject(s)
Medical Oncology , Humans , Medical Oncology/economics , Health Workforce , Neoplasms/therapyABSTRACT
The clinical use of cell-free DNA (cfDNA) methylation in managing lung cancer depends on its ability to differentiate between malignant and healthy cells, assign methylation changes to specific tissue sources, and elucidate opportunities for targeted therapy. From a technical standpoint, cfDNA methylation analysis is primed as a potential clinical tool for lung cancer screening, early diagnosis, prognostication, and treatment, pending the outcome of elaborate validation studies. Here, we discuss the current state of the art in cfDNA methylation analysis, examine the unique features and limitations of these new methods in a clinical context, propose two models for applying cfDNA methylation data for lung cancer screening, and discuss future research directions.
Subject(s)
Biomarkers, Tumor , Cell-Free Nucleic Acids , DNA Methylation , Lung Neoplasms , Humans , Lung Neoplasms/genetics , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy , Cell-Free Nucleic Acids/genetics , Biomarkers, Tumor/genetics , Prognosis , Early Detection of Cancer/methods , Disease ManagementABSTRACT
Prostate cancer is the second most prevalent cancer in men globally. De novo neuroendocrine prostate cancer (NEPC) is uncommon at initial diagnosis, however, (treatment-induced) t-NEPC emerges in up to 25% of prostate adenocarcinoma (PRAD) cases treated with androgen deprivation, carrying a drastically poor prognosis. The transition from PRAD to t-NEPC is underpinned by several key genetic mutations; TP53, RB1, and MYCN are the main genes implicated, bearing similarities to other neuroendocrine tumours. A broad range of epigenetic alterations, such as aberrations in DNA methylation, histone post-translational modifications, and non-coding RNAs, may drive lineage plasticity from PRAD to t-NEPC. The clinical diagnosis of NEPC is hampered by a lack of accessible biomarkers; recent advances in liquid biopsy techniques assessing circulating tumour cells and ctDNA in NEPC suggest that the advent of non-invasive means of monitoring progression to NEPC is on the horizon. Such techniques are vital for NEPC management; diagnosis of t-NEPC is crucial for implementing effective treatment, and precision medicine will be integral to providing the best outcomes for patients.