An investigation of plasma cell-free RNA for the detection of colorectal cancer: From transcriptome marker selection to targeted validation.

Regular screening for colorectal cancer (CRC) is critical for early detection and long-term survival. Despite the current screening options available and advancements in therapies there will be around 53,000 CRC related deaths this year. There is great interest in non-invasive alternatives such as plasma cell-free RNA (cfRNA) for diagnostic, prognostic, and predictive applications.

Detection of low-level parental somatic mosaicism for clinically relevant SNVs and indels identified in a large exome sequencing dataset.

Background: Due to the limitations of the current routine diagnostic methods, low-level somatic mosaicism with variant allele fraction (VAF) < 10% is often undetected in clinical settings. To date, only a few studies have attempted to analyze tissue distribution of low-level parental mosaicism in a large clinical exome sequencing (ES) cohort.

Methods: Using a customized bioinformatics pipeline, we analyzed apparent de novo single-nucleotide variants or indels identified in the affected probands in ES trio data at Baylor Genetics clinical laboratories.

High Detection Rates of Pancreatic Cancer Across Stages by Plasma Assay of Novel Methylated DNA Markers and CA19-9.

Purpose: We have previously identified tissue methylated DNA markers (MDMs) associated with pancreatic ductal adenocarcinoma (PDAC). In this case-control study, we aimed to assess the diagnostic performance of plasma MDMs for PDAC.

Experimental Design: Thirteen MDMs (, and ) were identified on the basis of selection criteria applied to results of prior tissue experiments and assays were optimized in plasma.

Methylated DNA in Pancreatic Juice Distinguishes Patients With Pancreatic Cancer From Controls.

Background & Aims: Precursors of pancreatic cancer arise in the ductal epithelium; markers exfoliated into pancreatic juice might be used to detect high-grade dysplasia (HGD) and cancer. Specific methylated DNA sequences in pancreatic tissue have been associated with adenocarcinoma. We analyzed these methylated DNA markers (MDMs) in pancreatic juice samples from patients with pancreatic ductal adenocarcinomas (PDACs) or intraductal papillary mucinous neoplasms (IPMNs) with HGD (cases), and assessed their ability to discriminate these patients from individuals without dysplasia or with IPMNs with low-grade dysplasia (controls).

Novel Methylated DNA Markers Discriminate Advanced Neoplasia in Pancreatic Cysts: Marker Discovery, Tissue Validation, and Cyst Fluid Testing.

Objectives: Pancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy.

A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): demonstration with IsomiR profiling in colorectal neoplasia.

Background: MicroRNA (miRNA) profiling is an important step in studying biological associations and identifying marker candidates. miRNA exists in isoforms, called isomiRs, which may exhibit distinct properties. With conventional profiling methods, limitations in assay and analysis platforms may compromise isomiR interrogation.

Novel Approach to Fecal Occult Blood Testing by Assay of Erythrocyte-Specific microRNA Markers.

Background: Fecal occult blood testing (FOBT) has historically relied on methods to detect hemoglobin with no fundamental innovations in decades.

Aim: To examine microRNA (miRNA) as a new marker class for FOBT.

Methods: Candidate miRNA markers were identified by small RNA sequencing of human whole blood compared to colorectal epithelia.

MicroRNA-20a in human faeces as a non-invasive biomarker for colorectal cancer.

Objective: Detection of microRNA (miRNA) aberrations in human faeces is a new approach for colorectal cancer (CRC) screening. The aim of this study was to characterise miR-20a in faeces as a non-invasive biomarker for diagnosis of CRC.

Results: miR-20a expression was significantly higher in the 40 CRC tumours compared to their respective adjacent normal tissues (P = 0.

microRNA-139-5p exerts tumor suppressor function by targeting NOTCH1 in colorectal cancer.

Background: miR-139-5p was identified to be significantly down-regulated in colon tumor tissues by miRNA array. We aimed to clarify its biological function, molecular mechanisms and direct target gene in colorectal cancer (CRC).

Methods: The biological function of miR-139-5p was examined by cell growth, cell cycle and apoptosis analysis in vitro and in vivo.

Identification of microRNA-135b in stool as a potential noninvasive biomarker for colorectal cancer and adenoma.

Purpose: Detecting microRNA (miRNA) in stool is a novel approach for colorectal cancer (CRC) screening. This study aimed to identify stool-based miRNA as noninvasive biomarkers for detection of CRC and adenoma.

Experimental Design: A miRNA expression array covering 667 human miRNAs was performed on five pairs of CRC and two pairs of advanced adenoma tissues.

Tumor suppressor functions of miR-133a in colorectal cancer.

Unlabelled: Dysregulated microRNA (miRNA) expression was profiled through a miRNA array comparison between human colorectal cancer tumors and their adjacent normal tissues. Specifically, using laser capture micro-dissection, miR-133a was shown to be significantly downregulated in primary colorectal cancer specimens compared with matched adjacent normal tissue. Ectopic expression of miR-133a significantly suppressed colorectal cancer cell growth in vitro and in vivo.

Colorectal cancer screening: are stool and blood based tests good enough?

Colorectal cancer (CRC) is the third commonest cancer worldwide. As many CRC patients were identified at advanced stages, screening asymptomatic individuals has substantial clinical benefit. Most CRC arises through recognizable early stage.

MicroRNA-18a attenuates DNA damage repair through suppressing the expression of ataxia telangiectasia mutated in colorectal cancer.

Background: miR-18a is one of the most up-regulated miRNAs in colorectal cancers (CRC) based on miRNA profiling. In this study, we examined the functional significance of miR-18a in CRC.

Methods: Expression of miR-18a was investigated in 45 CRC patients.

MicroRNA-218 inhibits cell cycle progression and promotes apoptosis in colon cancer by downregulating BMI1 polycomb ring finger oncogene.

Deregulated miRNAs participate in colorectal carcinogenesis. In this study, miR-218 was found to be downregulated in human colorectal cancer (CRC) by miRNA profile assay. miR-218 was silenced or downregulated in all five colon cancer cells (Caco2, HT29, SW620, HCT116 and LoVo) relative to normal colon tissues.

Functional role of peroxisome-proliferator-activated receptor γ in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Major risk factors of HCC include infection with hepatitis B or C viruses, alcohol and non-alcoholic fatty liver disease. HCC is difficult to diagnose at early stage, and has a very poor survival rate when diagnosed at a late stage.

Detection of miR-92a and miR-21 in stool samples as potential screening biomarkers for colorectal cancer and polyps.

Objective: The detection of molecular markers in stool samples is a potential strategy for colorectal cancer (CRC) screening. This study evaluated the feasibility of detecting miR-21 and miR-92a in stool samples of patients with CRC or polyps.

Methods: The reproducibility of detection and stability of stool-based microRNA were evaluated.

Inhibitory role of peroxisome proliferator-activated receptor gamma in hepatocarcinogenesis in mice and in vitro.

Unlabelled: Although peroxisome proliferator-activated receptor gamma (PPARgamma) agonist have been shown to inhibit hepatocellular carcinoma (HCC) development, the role of PPARgamma in hepatocarcinogenesis remains unclear. We investigated the therapeutic efficacy of PPARgamma against HCC. PPARgamma-deficient (PPARgamma(+/-)) and wild-type (PPARgamma(+/+)) littermates were used in a diethylnitrosamine (DEN)-induced HCC model and treated with PPARgamma agonist (rosiglitazone) or the vehicle alone for 8 months.

Peroxisome proliferator-activated receptors gamma reverses hepatic nutritional fibrosis in mice and suppresses activation of hepatic stellate cells in vitro.

Nonalcoholic steatohepatitis with fibrosis is a more severe form of nonalcoholic fatty liver disease, one of the most common liver diseases. We have previously shown that peroxisome proliferator-activated receptors gamma (PPARgamma) ligand, rosiglitazone, prevented the development of the methionine choline deficient (MCD) diet-induced fibrosing steatohepatitis. We have now tested whether overexpression of PPARgamma ameliorates established steatohepatitis and fibrosis.