MiRNA expression profile in 3 sporadic young-onset and 2 late-onset Indian colorectal carcinoma patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE236991 | GEO | 2023/07/26
REPOSITORIES: GEO
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Project description:Background: The incidence of colorectal cancer (CRC) has been steadily increasing in younger individuals over the past several decades for reasons that are incompletely defined. Identifying differences in gene expression profiles, or transcriptomes, in early-onset colorectal cancer (EOCRC, < 50 years old) patients versus later-onset colorectal cancer (LOCRC, > 50 years old) patients is one approach to understanding molecular and genetic features that distinguish EOCRC. Methods: We performed RNA-sequencing (RNA-seq) to characterize the transcriptomes of patient-matched tumors and adjacent, uninvolved (normal) colonic segments from EOCRC (n=21) and LOCRC (n=22) patients. The EOCRC and LOCRC cohorts were matched for demographic and clinical characteristics. We used The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) database for validation. We used a series of computational and bioinformatic tools to identify EOCRC-specific differentially expressed genes, molecular pathways, predicted cell populations, differential gene splicing events, and predicted neoantigens. Results: We identified an eight-gene signature in EOCRC comprised of ALDOB, FBXL16, IL1RN, MSLN, RAC3, SLC38A11, WBSCR27 and WNT11, from which we developed a score predictive of overall CRC patient survival. On the entire set of genes identified in normal tissues and tumors, cell type deconvolution analysis predicted a differential abundance of immune and non-immune populations in EOCRC versus LOCRC. Gene set enrichment analysis identified increased expression of splicing machinery in EOCRC. We further found differences in alternative splicing (AS) events, including one within the long non-coding RNA, HOTAIRM1. Additional analysis of AS found seven events specific to EOCRC that encode potential neoantigens. Conclusion: Our transcriptome analyses identified genetic and molecular features specific to EOCRC which may inform future screening, development of prognostic indicators, and novel drug targets.
2024-04-11 | GSE251845 | GEO
Project description:AIM: To investigate whether chromosomal instability (CIN) is associated with tumor phenotypes and/or with global genomic status based on MSI (microsatellite instability) and CIMP (CpG island methylator phenotype) in early onset colorectal cancer (EOCRC). METHODS: Taking as a starting point our previous work in which tumors from 60 EOCRC cases (≤45 years at the time of diagnosis) were analyzed by array comparative genomic hybridization (aCGH), in the present study we performed an unsupervised hierarchical clustering analysis of those aCGH data in order to unveil possible associations between the CIN profile and the clinical features of the tumors. In addition, we evaluated the MSI and the CIMP statuses of the samples with the aim of investigating a possible relationship between copy number alterations (CNAs) and the MSI/CIMP condition in EOCRC. RESULTS: Based on the similarity of the CNAs detected, the unsupervised analysis stratified samples into two main clusters (A, B) and four secondary clusters (A1, A2, B3, B4). The different subgroups showed a certain correspondence with the molecular classification of colorectal cancer (CRC), which enabled us to outline an algorithm to categorize tumors according to their CIMP status. Interestingly, each subcluster showed some distinctive clinicopathological features. But more interestingly, the CIN of each subcluster mainly affected articular chromosomes, allowing us to define chromosomal regions more specifically affected depending on the CIMP/MSI status of the samples. CONCLUSIONS: Our findings may provide a basis for a new form of classifying EOCRC according to the genomic status of the tumors.
2019-12-20 | GSE108220 | GEO
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.
2014-08-04 | E-GEOD-39084 | biostudies-arrayexpress
Project description:Early-onset colorectal cancer (EOCRC; age younger than 50 years) incidence has been steadily increasing over the last decades worldwide with causes unexplained. A unique molecular feature of EOCRC is that these cases harbor a greater incidence of Nodal Modulator 1 (NOMO1) somatic deletions compared with late-onset CRC. Yet the mechanisms of NOMO1 in early-onset colorectal carcinogenesis are currently unknown. Here we show that 50% of heterozygous NOMO1 deleted–EOCRCs presented pathogenic mutations in this gene, suggesting that NOMO1 can be inactivated by deletion or mutation in EOCRC. To study its role in EOCRC, CRISPR/cas9 technology was used to generate NOMO1 knockout HCT-116 (EOCRC) and HS-5 (bone marrow) cell lines. Loss of NOMO1 in these cell lines did not perturb Nodal pathway signaling. Results from expression microarray, RNA sequencing and protein expression analysis by LC-IMS/MS revealed that NOMO1 inactivation deregulates other signaling pathways independent of the Nodal pathway such as epithelial-mesenchymal transition. Importantly, NOMO1 inactivation increased the migration capacity of CRC cells. Additionally, a gut-specific conditional KO mouse model of NOMO1 revealed no subsequent tumor development in mice. Overall, these findings suggest that NOMO1 could not be a driver of early-onset colorectal carcinogenesis, but its loss promotes an increased migration capacity of CRC cells. Further study is warranted to explore other signaling pathways deregulated by the loss of NOMO1 that may play a relevant role in the pathogenesis of the disease.
2022-10-15 | PXD033636 | Pride
Project description:Despite a decrease in the incidence of colorectal cancer (CRC) over the last 40 years, the incidence of CRC in people under 50 years old is increasing around the globe. Early onset (50 years old) and late onset (65 years old) CRC appear to have differences in their clinicopathological and genetic features, but it is unclear if there are differences in the tumor microenvironment. We hypothesized that the immune microenvironment of early onset CRC is distinct from late onset CRC and promotes tumor progression. We used Nanostring immune profiling to analyze mRNA expression of immune genes in FFPE surgical specimens from patients with early (N=40) and late onset (N=39) CRC. We found three genes, SAA1, C7, and CFD, have increased expression in early onset colorectal cancer and distinct immune signatures based on the tumor location. After adjusting for clinicopathological features, increased expression of CFD and SAA1 were associated with worse progression free survival and increased expression of C7 was associated with worse overall survival. We also performed gain of function experiments with CFD and SAA1 in subcutaneous tumor murine models and found that CFD is associated with higher tumor volumes, impacted several immune genes and impacted three genes in mice that were also found to be differentially expressed in early onset CRC (EGR1, PSMB9, CXCL9). Our data demonstrate that the immune microenvironment, characterized by a distinct innate immune response signature in early onset CRC, is unique, location dependent, and might contribute to worse outcomes.
2021-05-25 | GSE175433 | GEO
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.
2014-08-04 | GSE39084 | GEO
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.
2011-09-06 | E-GEOD-25071 | biostudies-arrayexpress
Project description:Despite a global decrease in colorectal cancer (CRC) incidence, the prevalence of early onset colorectal cancer (EOCRC), or those occurring in individuals before the age of 50, has been steadily increasing over the past several decades. When compared to later onset colorectal cancers (LOCRCs) in individuals over 50, our understanding of the genetic and molecular underpinnings of EOCRCs is limited. Here, we conducted transcriptomic analysis of patient-matched normal colonic segments and tumors to identify gene expression programs involved in carcinogenesis. Amongst differentially expressed genes, we found increased expression of the c-MYC (MYC) proto-oncogene and its downstream targets in tumor samples. We identify tumors with high and low differential MYC expression, and patients with high-MYC tumors were older and overweight or obese. We also detect elevated expression of the PVT1 long-non-coding RNA (lncRNA) in most tumors and find gains in copy number for both MYC and PVT1 gene loci in 35% of tumors evaluated. Our transcriptome analysis indicates that EOCRC can be sub-classified into groups based on differential MYC expression and suggests that MYC is a critical driver of most CRCs that develop in younger patients.
2022-09-06 | GSE196006 | GEO
Project description:An increase in early-onset colorectal cancers (eoCRC), defined as a CRC before 50 years, is confirmed globally.
CRC pathogenesis has been associated with several risk factors (family history, germline pathogenic variants, obesity, alcohol, physical activity, red meat, and a Western diet).
Design: an international, multicenter, retrospective case-control study of prospectively enrolled patients; low-risk intervention study as it will perform a fecal occult blood test Endpoint: predictive power of a semi-quantitative food frequency questionnaire (SQFFQ) developed for eoCRC.
Cases: Patients with a recent diagnosis of eoCRC (within 2 years from enrollment).
Controls: matched by age (matching range ± 5 years) and sex. Healthy volunteers will be mainly enrolled among workers within the participating hospital center. The enrolled healthy volunteers will perform a fecal occult blood test.
Variables of interest: age, sex, ethnicity, BMI at the time of eoCRC diagnosis and at 18 years old, country, tobacco smoking at the time of eoCRC diagnosis and at 18 years old, sitting time, TV-viewing time, moderate-to-vigorous physical activity (MVPA), waist circumference (cm), home blood pressure levels (mmHg), fasting blood glucose (mg/dl), regular consumption of aspirin/NSAID, calcium and folate supplements, oral contraceptive agents, post-menopausal hormones and years of consumptions, if the filled questionnaire reflects diet for the last 5-10 years before.
Cases only: date of eoCRC diagnosis, symptoms at diagnosis, eoCRC localization, eoCRC stage, histological diagnosis, type of surgery, and date (if performed), chemotherapy and radiotherapy (if performed), vital status and duration of follow-up, family history of CRC and other cancers (uterus, ovary, stomach, small intestine, urinary tract/bladder/kidney, bile ducts, brain, pancreas, skin tumors), type of germline pathogenetic variant (if performed).
Before the case-control study, three non-consecutive 24-hour Dietary Recalls (24hDRs) will validate the SQFFQ.
The SQFFQ will be administered to the validation study group during three non-consecutive calls, including one non-weekday (30-minute 24-h-recall computer-aided personal interview).
Primary Objective To measure the relative risk of specific dietary and lifestyle factors (smoking habit, alcohol intake, physical activity) for early-onset colorectal cancer in countries where eoCRC incidence is increasing versus stable/decreasing
| 8689 | ecrin-mdr-crc
Project description:Background. The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the United States, and EOCRC disproportionately affects racial/ethnic minorities. Here, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Hispanic and African American patients. Results. We show the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer (LOCRC) patients, and methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways. Furthermore, we identify epigenetic alterations in metabolic genes that are specific to our racial/ethnic minority EOCRC cohort but not Caucasian patients from TCGA. Top genes differentially methylated between these cohorts included the obesity-protective MFAP2 gene as well as cancer risk susceptibility genes APOL3 and RNASEL. Conclusions. In this study, we provide to the scientific community high-resolution DNA methylomes for a cohort of EOCRC patients from underrepresented populations. Our exploratory findings in this cohort highlight epigenetic mechanisms underlying the pathogenesis of EOCRC and nominate novel biomarkers for EOCRC in underrepresented populations.
2025-01-29 | GSE284325 | GEO