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Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-associated Immunity in Lynch Syndrome patients [GeoMx Digital Spatial Profiling (DSP)]

ABSTRACT: This CYCling Lynch patients for Exercise and Prevention (CYCLE-P) trial was a prospective, non-randomized controlled trial conducted at the Familial High-Risk Gastrointestinal and Cancer Prevention Clinic of The University of Texas MD Anderson Cancer Center. Twenty-one LS participants with a confirmed pathogenic mutation in one of four DNA mismatch repair (MMR) genes were enrolled between April 2018 and January 2019. Follow-up was conducted 1-year from the start of the intervention. Statistical analysis by both per-protocol and intention-to-treat was performed from March to May 2021.

ORGANISM(S): Homo sapiens

PROVIDER: GSE210011 | GEO | 2023/08/07

REPOSITORIES: GEO

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Exercise Training Influences Inflammatory and Immune Systems in Patients at High Risk for Colorectal Cancer: The CYCLE-P Study

Project description:This CYCling Lynch patients for Exercise and Prevention (CYCLE-P) trial was a prospective, non-randomized controlled trial conducted at the Familial High-Risk Gastrointestinal and Cancer Prevention Clinic of The University of Texas MD Anderson Cancer Center. Twenty-one LS participants with a confirmed pathogenic mutation in one of four DNA mismatch repair (MMR) genes were enrolled between April 2018 and January 2019. Follow-up was conducted 1-year from the start of the intervention. Statistical analysis by both per-protocol and intention-to-treat was performed from March to May 2021.

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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.

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Genomic profiling of colorectal cancer from patients with Lynch syndrome and Familial colorectal cancer type X with comparison to sporadic microsatelite stable and instable colorectal cancer

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