Project description:aCGH experiment on cell-free DNA collected from the plasma of patients with castration-resistant prostate cancer. No replicates. castration-resistant prostate cancer vs male reference DNA
Project description:Cell-free RNA (cfRNA) in plasma reflects gene expression profiles of both localized sites of cancer and at the systemic host response. Here we explore the diagnostic potential of cell-free transcriptomes by mRNA sequencing. We sequenced total cell-free plasma RNA from 90 plasma samples from two independent sample cohorts representing two cancer types, two pre-cancerous conditions and non-cancer donors. We identified distinct gene sets and built classification models that could distinguish cancer patients with specific cancer types from premalignant conditions and non-cancer individuals with high accuracy. Determination of multiple myeloma from its pre-cancerous monoclonal gammopathy of undetermined significance (MGUS) yielded an accuracy of 90% (17/19). Detection of primary liver cancer from its premalignant condition cirrhosis yielded an accuracy of 100% (12/12). This work lays the foundation for developing low cost assays by measuring mRNA transcript levels in plasma using a small panel of genes for detection that can distinguish the presence of cancer from pre-cancerous conditions and non-cancer individuals.
Project description:We sequenced cell-free RNA (cfRNA) for five cancer types (colorectal cancer, stomach cancer, liver cancer, lung cancer and esophageal cancer) and healthy individuals in 230 plasma samples collected from 6 clinical centers in China. Cancer related signaling pathway and microbial genus were identified. Cancer detection and specific classification were achieved through combining both host and microbial cfRNA reads.
Project description:We performed RNA-Seq analysis of plasma and urinary EVs collected before and after radical prostatectomy, and matched tumor and normal prostate tissues of 10 patients with prostate cancer. To identify putative cancer-derived RNA biomarkers, we searched for RNAs that were overexpressed in tumor as compared to normal tissues, present in the pre-operation EVs and decreased in the post-operation EVs in each RNA biotype.
Project description:We used a highly sensitive nano-5hmC-Seal method and profiled the genome-wide distribution of 5-hydroxymethylcytosine (5hmC) in plasma cell-free DNA (cfDNA) from 384 patients with bladder, breast, colorectal, kidney, lung, or prostate cancer and 221 controls. We used machine learning and developed plasma cfDNA 5hmC signatures that are highly sensitive for cancer detection and cancer origin determination. We also identified genes and signaling pathways with aberrant DNA hydroxymethylation in six cancers.
Project description:Castration-resistant prostate cancer (CRPC) is a heterogeneous disease associated with phenotypic subtypes that drive differences in therapy response and outcomes. Histologic transformation to castration-resistant neuroendocrine prostate cancer (CRPC-NE) is associated with distinct epigenetic alterations, including acquired changes in DNA methylation. The current diagnosis of CRPC-NE is challenging and relies on metastatic biopsy. Here, we developed a targeted DNA methylation assay based on the analysis of large tissue datasets to detect CRPC-NE using plasma cell-free DNA (cfDNA) non-invasively. The assay quantifies tumor content and a phenotype evidence score that captures the spectrum of CRPC phenotypes, leveraging a few hundred informative genomic regions to also inform the expression and/or transcriptional state of genes of interest. We qualified the assay in independent clinical cohorts, including 158 plasma samples, achieving a phenotypic evidence score AUC > 0.93 for detecting pathology-confirmed CRPC-NE, and revealing associations between methylation-defined tumor content and clinical outcomes in two prospective phase 2 clinical trials (NCT01799278 and NCT00514540) designed toward aggressive variant CRPC and CRPC-NE, supporting the application of targeted DNA methylation for CRPC-NE detection and patient stratification.