Project description:We attempted to screen and identify new plasma EV delivered microRNA can simultaneously diagnose AA, early CRC and advanced CRC in healthy people. We employed microRNA deep sequencing assay for the primary screen and performed TaqMan microRNA assay for further test and validation. Through stepwise screen and validation in two independent cohorts (cohort I: n=75, cohort II: n=104), we demonstrated that plasma EV-delivered miR-185-5p is a potential indicator of AA and CRC in Chinese patients. In the supplementary phase, we also preliminarily proved that miR-185-5p can promote the development of CRC in vivo and in vitro.
2023-09-11 | GSE220445 | GEO
Project description:Stool shotgun metagenomic profiles CRC patients and healthy controls - TU cohort
Project description:Extracellular vesicles (EVs) are valuable sources for the discovery of useful cancer biomarkers. This study explores the potential usefulness of tumor cell-derived EV membrane proteins as plasma biomarkers for early detection of colorectal cancer (CRC). EVs were isolated from the culture supernatants of four CRC cell lines by ultracentrifugation, and their protein profiles were analyzed by LC-MS/MS. Bioinformatics analysis of identified proteins revealed 518 EV membrane proteins in common among at least three CRC cell lines. We next used accurate in-clusion mass screening (AIMS) in parallel with iTRAQ-based quantitative proteomic analysis to highlight candidate proteins and validated their presence in pooled plasma-generated EVs from 30 healthy controls and 30 CRC patients. From these, we chose 14 potential EV-derived targets for further quantification by targeted MS assay in a separate individual cohort comprising of 73 CRC and 80 healthy subjects. Quantitative analyses revealed significant increases in ADAM10, CD59 and TSPAN9 levels (2.19- to 5.26-fold, p <0.0001) in plasma EVs from CRC patients, with AUC values of 0.83, 0.95 and 0.87, respectively. Higher EV CD59 levels were significantly corre-lated with distant metastasis (p = 0.0475), and higher EV TSPAN9 levels were significantly asso-ciated with lymph node metastasis (p = 0.0011), distant metastasis at diagnosis (p = 0.0104) and higher TNM stage (p = 0.0065). A two-marker panel consisting of CD59 and TSPAN9 outper-formed the conventional marker CEA in discriminating CRC and stage I/II CRC patients from healthy controls, with AUC values of 0.98 and 0.99, respectively. Our results identify EV mem-brane proteins in common among CRC cell lines and altered plasma EV protein profiles in CRC patients, and suggest plasma EV CD59 and TSPAN9 as a novel biomarker panel for detecting early-stage CRC.
Project description:In this study, we conducted a microarray-based analysis to identify differentially expressed miRNAs in CRC by comparing miRNA profiles among primary CRC tissues from patients with liver metastases, primary tissues without liver metastases, and liver metastatic lesions. microRNAs (miRNAs) have been shown to have a potential for cancer diagnosis lately. The main objective of this study is to identify a novel biomarker serum miRNA from the patients with colorectal cancer (CRC). Microarray analysis of miRNA expression was performed using paired pre- and post- operative serum from 10 CRC patients. Two miRNAs (let-7a, miR-199a-3p) decreased significantly in the post-operative serum when compared to pre-operative serum (P=0.015 and 0.029, respectively). Microarrays were performed for the testing cohort of primary CRC lesions (n=28) and liver metastatic lesions (n=8).
Project description:EPIC array data were generated from 2 MDD case control cohorts. EWAS was performed in each cohort, followed by meta-analysis between the 2 cohort. Cohort 1: A total of 191 blood samples from 112 patients with MDD was collected up till the interim analysis (wave 1 samples) from an observational clinical study OBSERVEMDD0001 (ClinicalTrials.gov Identifier: NCT02489305) compared to 32 healthy controls; Cohort 2: The MDD cases (N = 359) were drawn from the Molecular Biomarkers of Antidepressant Response study compared to 68 healthy controls.
Project description:Here, we present the first study showing race and side-specific differences in the trajectories of epigenetic aging in normal colonic mucosa. The cohort conisted of matched biopsies of left/right colon from healthy individuals (n=129). The majority of individuals were African American (n=89). Methylation arrays (Illumina EPIC) were performed on DNA extracted from fresh frozen biopsies taken at the time of colonoscopy. Our results provide novel insight of epigenetic aging underlying racial disparities in CRC. Side-specific colonic epigenetic aging may be a promising marker to guide interventions to reduce CRC burden.
Project description:Disrupted interactions between host and intestinal bacteria are implicated in the development of colorectal cancer (CRC). However, the functional impacts of these inter-kingdom interactions remain poorly defined. To examine this interplay, we performed small RNA sequencing on the stool of from germ-free (GF) and gnotobiotic ApcMin/+;Il10-/- mice associated with microbes from biofilm-positive human CRC tumor (BT) and biofilm-negative healthy (BX) tissues. revealed a group of significant differentially expressed miRNAs specific to BT compared to BX associated ApcMin/+;Il10-/- mice and several miRNAs that correlated with bacterial genera abundances. Our findings suggest complex interactions within bacterial communities affecting host-derived miRNA and CRC development.