Project description:Liver cancer is one of the most lethal cancers worldwide. Liquid biopsy provides a noninvasive approach in detecting and monitoring cancer biomarkers to overcome current limitations associated with tissue biopsies, comprising the analysis of circulating tumor-derived material. In this study, we profiled plasma cell-free RNA-seq to identify recurrently dysregulated RNA biomarkers for the liquid biopsy of cancer.
Project description:Liquid biopsies offer significant potential for informing on cancer progression and therapeutic resistance via minimally invasive serial monitoring of genetic alterations. Although the cancer epigenome is a central driving force in most neoplasia, how well the tumour methylome can be monitored via liquid biopsies is relatively unknown. In this first of its kind study we made a direct comparison of two liquid biopsies: urine and blood, asking how well they represent the tumor methylome. Utilizing the Infinium Methylation EPIC BeadChip, we profiled DNA methylation in tissue, urine sediment and cell-free circulating DNA from four men with advanced stage prostate cancer. We show that both urine and plasma are viable surrogates for tumor tissue biopsies, capturing 78.63 and 62.21% of tumor-specific methylation alterations, respectively. We conclude that urine is an easily accessible and sensitive biofluid for the study of prostate cancer epigenomic alterations.
Project description:Liquid biopsies are gaining more traction as non-invasive tools for the diagnosis and monitoring of cancer. A new class of cancer therapeutics, synergistic botanical drug combinations (APG-157) can target multiple pathways and provide a durable response and safety. Monitoring the efficacy of such drugs involves assessing multiple molecules and cellular events simultaneously. We report a methodology using plasma cell-free RNA (cfRNA) as an indicator of patient response during drug treatment. Plasma was collected from six patients with head and neck cancer (HNC) and four controls receiving APG-157 or placebo through an oral mucosal route, before treatment and on multiple points post-dosing. Circulating cfRNA was extracted from plasma at 0-, 3- and 24-hours post-treatment, followed by RNA sequencing. Analysis of the circulating transcriptome pointed to significant perturbations following APG-157 treatment. Transcripts associated with inflammatory response and leukocyte activation were upregulated upon treatment with APG-157 in cancer patients, but not in controls or placebo-treated patients. A platelet-related transcriptional signature could be detected in patients but not in controls, indicating a platelet-centric pathway in HNC. These results from a Phase 1 study are a proof of principle of the utility of cfRNAs as non-invasive biomarkers for monitoring the efficacy of APG-157 in HNC.
Project description:Deacetylation of HP1g enhances multiple myeloma drug resistance through DNA damage repair and liquid-liquid phase separation (RNA-Seq)
Project description:Deacetylation of HP1g enhances multiple myeloma drug resistance through DNA damage repair and liquid-liquid phase separation (ChIP-seq)
Project description:Deacetylation of HP1g enhances multiple myeloma drug resistance through DNA damage repair and liquid-liquid phase separation (ATAC-Seq)
