Project description:Colorectal cancer (CRC) incidence increases with age and early onset of the disease is an indication of genetic predisposition, estimated to cause up to 30 % of all CRC cases. To identify genes associated with an increased risk for CRC, genome-wide gene expression levels of CRCs from patients diagnosed at an early age and CRCs from patients diagnosed at higher age were investigated. Patients with known hereditary predisposition syndromes were excluded from the study.
Project description:Colorectal cancer (CRC) incidence increases with age and early onset of the disease is an indication of genetic predisposition, estimated to cause up to 30 % of all CRC cases. To identify genes associated with an increased risk for CRC, genome-wide gene expression levels of CRCs from patients diagnosed at an early age and CRCs from patients diagnosed at higher age were investigated. Patients with known hereditary predisposition syndromes were excluded from the study. Twenty four patients were diagnosed at a young age (mean, 43 years; range, 28-53 years), referred to as the early onset group. They were excluded from the HNPCC and FAP syndromes by clinical criteria and no other cancer syndromes were recorded for these patients. The second group consisted of 17 patients with primary diagnosis at old age (mean, 79 years; range, 69-87 years), referred to as the late onset group. The samples from the late onset group were selected to reflect the composition of the early onset group with respect to gender, tumor localization and tumor stage according to The International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC). Microsatellite instability (MSI) status was previously analyzed in all samples to eliminate the potential risk of including patients with inherited DNA repair deficiencies.
Project description:To characterize proteomic signatures of platelet-derived medium-size EVs(mEVs) EVs of Colorectal cancer patients vs. healthy subjects (HS) matched for sex and age
Project description:Epigenetic clocks can quantify DNA methylation by measuring the methylation levels at specific sites in the genome, which correlate with biological age (BA). Accelerated aging, where BA exceeds chronological age (CA), has been studied in relation to cancer development, but its utility in cancer prevention remains unclear. Accelerated aging holds promise as a tool to explain the rise in early onset colorectal cancer (EOCRC). We investigate the association of accelerated aging and the presence of pre-neoplastic polyps (PNP) in the colon, defined as tubular adenomas and sessile serrated adenomas. In this study of persons under age 50 undergoing colonoscopy, we used peripheral blood samples to determine BA and age acceleration metrics. Age acceleration was determined by interrogating DNA methylation (DNAm) at specific CpG sites across the genome, which has been shown to correlate with age. We then conducted logistic regression analyses to evaluate the association between age acceleration and PNPs. In total, 51 patient samples were evaluated. We found that that the odds of harboring a PNP are 17% higher with 1 year of accelerated aging, as measured by GrimAge. However, the strongest risk factor for PNPs remained male sex. This represents one of the first studies to explore accelerated aging and PNP in patients under the age of 50. A risk-stratified approach to EOCRC screening would minimize unnecessary colonoscopies and minimize healthcare burden while addressing the rise in EOCRC. Our findings suggest that BA calculations with peripheral blood collections could be an important component of such a risk model.
Project description:Endometrial cancer had a relatively high prevalence of MMR deficiency. MMR-D/MSI-H endometrial cancer patients are suggested to be potential beneficiaries of PD-1/PD-L1 inhibitor therapy. Here, we explored the prognostic value of MSI subtype in endometrial cancer and its correlation with immune environment. Based on expression and clinical data of 78 POLE, 123 MSI and 299 Other EC samples from the TCGA-UCEC project, we found that the MSI tumors were identified more often in early stage, had a lower age, better patient survival, enriched CD8+ T cells, and regulatory T cells and less M2 macrophages and activated dendritic cells than the Other group, and shared a relatively similar expression profile with POLE group by differential analysis. In addition, we established the immune landscape of an MMR-D endometrial cancer tissue using unbiased single-cell RNA-seq analysis of 3371 cells. By immunohistochemistry analysis, we found that the MMR-D tumors showed a higher trend of CD20+ B cells infiltration. Our study might expand our understanding of the role of immune subsets in MSI endometrial carcinomas and provide guidance of immunotherapy for endometrial cancer.
Project description:In order to improve the understanding of the impact of sex during colorectal cancer development we sequenced, for the first time, the colonic epithelium of wild-type mice of both sexes treated with 9 or 15 weeks AOM/DSS.
Project description:Sporadic early onset colorectal carcinoma (EOCRC) is a growing problem that remains poorly understood. Clinical specificities and mechanisms of tumorigenesis might be relevant to both diagnosis and treatment. In this prospective study, clinicopathological features, genomic and gene expression profiles of sporadic EOCRC were compared to other well defined groups of CRC. Seventy selected patients were divided into 4 groups according to age (< 45 or > 60 years) and mismatch repair status. Mutations of key genes involved in colorectal carcinogenesis (P53, KRAS, BRAF, PIK3CA) were detected and the methylator phenotype (CIMP) established. Gene expression profiles (GEP) were obtained using pangenomic Affymetrix GeneChip.