Systemic circulating microRNA landscape in Lynch syndrome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA817160 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18345000.fastq.gz | Fastqsanger.gz | |||
| SRR18345100.fastq.gz | Fastqsanger.gz | |||
| SRR18345200.fastq.gz | Fastqsanger.gz | |||
| SRR18345300.fastq.gz | Fastqsanger.gz | |||
| SRR18345400.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: Lynch syndrome (LS) is a hereditary cancer syndrome. Systemic circulating microRNA expression levels (c-miRnome) in LS carriers have not been characterized previously. This exploratory study characterized the systemic c-miRnomes of LS carriers with or without cancer and compared it to c-miRnomes of sporadic rectal cancer patients and healthy controls. Methods: Blood serum samples of Lynch syndrome carriers without (n=81) or with (n=13) cancer, sporadic rectal cancer patients (n=24) and healthy controls (n=37) were sequenced with NextSeq500. FastQC was used for quality controls. High quality samples with Phred score >25 were selected for downstream analysis. FastX-toolkit was used for trimming and filtering. Mapping of the reads to miRbase (v.22) was conducted with Bowtie with v-mode and best strata parameters for single-end data. Only the uniquely mapped reads were selected for differential expression (DE) analysis. Dimension reduction analysis was conducted with t-SNE. Target gene prediction and pathway analysis was performed with mirWalk and validated with COSMIC-database. Results: An average of 3.2M reads pers sample was achieved. We identified a pool of 228 c-miRs common to all study groups that was used to setup the design matrix for DE analysis. We identified a c-miRnome of 40 DE c-miRs that discern healthy LS carriers from healthy controls but could not distinguish them from cancer patients with or without LS. Our results suggested that hereditary and sporadic carcinogenesis share common biological pathways and alterations in these pathways generate a c-miR response, which can be used to track oncogenic stress at cancer-free state in LS. Conclusion: Our results show that c-miRs hold diagnostic and predictive potential in molecular profiling of human cancers.
2022-04-25 | GSE198834 | GEO
Project description:Circulating microRNAs (c-miRs) are small noncoding RNA molecules that migrate throughout the body and regulate gene expression. Global c-miR expression patterns (c-miRnomes) change with sporadic carcinogenesis and have predictive potential in early detection of cancers. However, there are no studies that have assessed whether c-miRnomes display similar potential in carriers of inherited pathogenic mismatch-repair gene variants (path_MMR), known as Lynch syndrome (LS), who are predisposed to highly increased cancer risk. Using high-throughput sequencing and bioinformatic approaches, we conducted an exploratory analysis to characterize systemic c-miRnomes of path_MMR carriers, sporadic rectal cancer patients and non-LS controls. We showed for the first time that cancer-free path_MMR carriers have a systemic c-miRnome of 40 differentially expressed c-miRs that can distinguish them from non-LS controls. The systemic c-miRnome of cancer-free path_MMR carriers also resembles the systemic c-miRnomes of cancer patients with or without path_MMR. Our pathway analysis linked the found differentially expressed c-miRs to carcinogenesis. A total of 508 putative target genes were identified for 32 out of 40 differentially expressed c-miRs, and 238 of them were enriched in cancer-related pathways. The most enriched c-miR-target genes include well-known oncogenes and tumor suppressor genes such as BCL2, AKT3, PIK3CA, KRAS, NRAS, CDKN1A and PIK3R1. Taken together, our findings suggest that LS and sporadic carcinogenesis share common biological pathways and alterations in these pathways can produce a c-miR signature which can track potential oncogenic stress in cancer-free path_MMR carriers. Therefore, c-miRs hold potential in monitoring the LS risk stratification patterns during clinical surveillance or cancer management.
| S-EPMC10092425 | biostudies-literature
Project description:Heredity is a major cause of ovarian cancer. Lynch syndrome is associated with 10-12% risk of ovarian cancer, diagnosis at young age and a predilection for endometrioid and clear cell tumors. Global gene expression profiling applied to 25 Lynch syndrome-associated and 42 sporadic ovarian cancers revealed 335 differentially expressed genes and involvement of the mTOR and the MAPK/ERK pathways. The clear cell tumors had distinct expression profiles with upregulation of HER2 and apoptosis signaling pathways. The distinct expression profiles provide clues relevant for hereditary tumorigenesis and may be relevant for therapeutic strategies and refined diagnostics in ovarian cancer linked to Lynch syndrome. Ovarian cancers linked to Lynch syndrome (n=25) were compared to a matched series of sporadic ovarian cancers (n=42), selected from a population-based consecutive series in which hereditary was excluded based on family history, normal MMR protein staining and lack of mutations in BRCA1 and BRCA2.
2013-10-14 | E-GEOD-37394 | biostudies-arrayexpress
Project description:Colorectal carcinomas arising in the context of Lynch syndrome, the most common inherited cancer syndrome, typically show deficiency of the DNA MMR (mismatch repair) system. Lack of functional MMR leads to accumulation of frameshift mutations at micosatellites (microsatellite instability, MSI). High load of highly immunogenic tumor-specific frameshift neoantigens results in strong immune response against Lynch syndrome MSI cancers. Previous studies have shown systemic immune responses against frameshift neoantigens in Lynch syndrome carriers long before tumor manifestation. In the present study, we analyzed the immune profile of normal colorectal mucosa in Lynch syndrome carriers without current or previous cancer history and in Lynch syndrome colorectal cancer patients, as well as of Lynch syndrome colorectal carcinomas. The unsupervised cluster analysis of gene expression data revealed a sharp differentiation between normal mucosa from Lynch syndrome individuals with and without manifest cancer as well as between normal mucosa in general and Lynch syndrome cancer tissue. Deconvolution analysis for predicting the prevalence of immune cell population among the three groups revealed 10 out of 14 investigated populations to be significantly different between the three tissue types (FDR=10%). In contrast to normal mucosa samples, tumor tissue showed overrepresentation of immune-suppressive cell populations, such as regulatory T cells and neutrophils. Taken together with the quantitative T cell density analysis on the basis of immunohistochemical T cell stainings, our data show strong immune infiltration of the normal colorectal mucosa in Lynch syndrome individuals even in the absence of a manifest cancer.
2022-03-14 | GSE178516 | GEO
Project description:We aimed to provide a molecular description of Lynch syndrome-associated urothelial cancer in relation to molecular subtypes of sporadic bladder cancer. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with data from sporadic bladder cancer.
2019-01-01 | GSE104922 | GEO
Project description:mRNA expression from adenomas of patients with Lynch Syndrome and Familial Adenomatous Polyposis
2018-04-16 | GSE106500 | GEO
Project description:Heredity is a major cause of ovarian cancer. Lynch syndrome is associated with 10-12% risk of ovarian cancer, diagnosis at young age and a predilection for endometrioid and clear cell tumors. Global gene expression profiling applied to 25 Lynch syndrome-associated and 42 sporadic ovarian cancers revealed 335 differentially expressed genes and involvement of the mTOR and the MAPK/ERK pathways. The clear cell tumors had distinct expression profiles with upregulation of HER2 and apoptosis signaling pathways. The distinct expression profiles provide clues relevant for hereditary tumorigenesis and may be relevant for therapeutic strategies and refined diagnostics in ovarian cancer linked to Lynch syndrome.
2013-10-14 | GSE37394 | GEO
Project description:Lynch syndrome and Familial colorectal cancer type X (FCCTX) are clinically diagnosed using the same criteria, but genomic differences exist between these two groups and the genomic profiles share similarities with their sporadic counterparts, mismatch repair (MMR) deficient and proficient tumors, respectively. Array-based comparative genomic hybridization was performed on 91 tumors, comprising 23 Lynch syndrome (AH), 23 FCCTX (AA), 23 sporadic MMR deficient (AM) and 22 sporadic MMR proficient tumors, in order to identify differences between Lynch syndrome and FCCTX.
2012-06-01 | E-GEOD-38405 | biostudies-arrayexpress
Project description:Faecal Microbiota Characterization in Lynch Syndrome (LS) Patients With or Without Colorectal Neoplasia ( AAS-Lynch-Microbiote)
| PRJEB70919 | ENA
Project description:Circulating metabolites systemically reflect cellular processes and can modulate the tissue microenvironment in complex ways, potentially impacting cancer initiation processes. Genetic background increases cancer risk in individuals with Lynch syndrome; however, not all carriers develop cancer. Various lifestyle factors can influence Lynch syndrome cancer risk, and lifestyle choices actively shape systemic metabolism, with circulating metabolites potentially serving as the mechanical link between lifestyle and cancer risk. This study aims to characterize the circulating metabolome of Lynch syndrome carriers, shedding light on the energy metabolism status in this cancer predisposition syndrome.This study consists of a three-group cross-sectional analysis to compare the circulating metabolome of cancer-free Lynch syndrome carriers, sporadic colorectal cancer (CRC) patients, and healthy non-carrier controls. We detected elevated levels of circulating cholesterol, lipids, and lipoproteins in LS carriers. Furthermore, we unveiled that Lynch syndrome carriers and CRC patients displayed similar alterations compared to healthy non-carriers in circulating amino acid and ketone body profiles. Overall, cancer-free Lynch syndrome carriers showed a unique circulating metabolome landscape.This study provides valuable insights into the systemic metabolic landscape of Lynch syndrome individuals. The findings hint at shared metabolic patterns between cancer-free Lynch syndrome carriers and CRC patients.
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