Differential Expression of PEG10 Contributes to Aggressive Disease in Early Versus Late-Onset Colorectal Cancer.
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ABSTRACT:
SUBMITTER: Watson KM
PROVIDER: S-EPMC7653836 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To identify the gene expression of early-onset colorectal cancer, we sampled early-onset colorectal cancer patients (age < 50) and late-onset colorectal cancer paitients (age > 70) We then performed gene expression profiling analysis using data obtained from RNA-seq of early-onset colorectal cancer tissues and late-onset colorectal cancer tissues.
2023-02-08 | GSE213092 | GEO
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:Early onset colorectal cancer tissues and late onset colorectal cancer tissues
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Project description:Co-pathologies play an important role in the expression of the Alzheimer's disease clinical phenotype and may influence treatment efficacy. Early-onset Alzheimer's disease, defined as manifesting before age 65, is viewed as a relatively pure form of Alzheimer's disease with a more homogeneous neuropathological substrate. We sought to compare the frequency of common neuropathological diagnoses in a consecutive autopsy series of 96 patients with early-onset Alzheimer's disease (median age of onset = 55 years, 44 females) and 48 with late-onset Alzheimer's disease (median age of onset = 73 years, 14 females). The UCSF Neurodegenerative Disease Brain Bank database was reviewed to identify patients with a primary pathological diagnosis of Alzheimer's disease. Prevalence and stage of Lewy body disease, limbic age-related TDP-43 encephalopathy (LATE), argyrophilic grain disease, hippocampal sclerosis, cerebral amyloid angiopathy, and vascular brain injury were compared between the two cohorts. We found at least one non-Alzheimer's disease pathological diagnosis in 98% of patients with early-onset Alzheimer's disease (versus 100% of late onset), and the number of comorbid diagnoses per patient was lower in early-onset than in late-onset Alzheimer's disease (median = 2 versus 3, Mann-Whitney Z = 3.00, P = 0.002). Lewy body disease and cerebral amyloid angiopathy were common in both early and late onset Alzheimer's disease (cerebral amyloid angiopathy: 86% versus 79%, Fisher exact P = 0.33; Lewy body disease: 49% versus 42%, P = 0.48, respectively), although amygdala-predominant Lewy body disease was more common in early than late onset Alzheimer's disease (22% versus 6%, P = 0.02). In contrast, LATE (35% versus 8%, P < 0.001), hippocampal sclerosis (15% versus 3%, P = 0.02), argyrophilic grain disease (58% versus 41%, P = 0.052), and vascular brain injury (65% versus 39%, P = 0.004) were more common in late than in early onset Alzheimer's disease, respectively. The number of co-pathologies predicted worse cognitive performance at the time of death on Mini-Mental State Examination [1.4 points/pathology (95% confidence interval, CI -2.5 to -0.2) and Clinical Dementia Rating-Sum of Boxes (1.15 point/pathology, 95% CI 0.45 to 1.84)], across early and late onset cohorts. The effect of sex on the number of co-pathologies was not significant (P = 0.17). Prevalence of at least one APOE ε4 allele was similar across the two cohorts (52% and 54%) and was associated with a greater number of co-pathologies (+0.40, 95% CI 0.01 to 0.79, P = 0.047), independent of age of symptom onset, sex, and disease duration. Females showed higher density of neurofibrillary tangles compared to males, controlling for age of onset, APOE ε4, and disease duration. Our findings suggest that non-Alzheimer's disease pathological diagnoses play an important role in the clinical phenotype of early onset Alzheimer's disease with potentially significant implications for clinical practice and clinical trials design.
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Project description:Investigators report greater parietal tau deposition and alternate frontoparietal network involvement in early onset Alzheimer's Disease (EOAD) with onset <65 years as compared with typical late onset AD (LOAD). To determine whether clinical brain MRI volumes reflect these differences in EOAD compared with LOAD. This study investigated the clinical MRI scans of 45 persons with Clinically Probable AD with onset <65 years, and compared them to 32 with Clinically Probable AD with onset ≥65 years. Brain volumes on their T1 MRI scans were quantified with a volumetric program. Receiver operating curve analyses were performed. Persons with EOAD had significantly smaller parietal lobes (volumetric percentiles) than LOAD. Late onset Alzheimer's Disease had a smaller left putamen and hippocampus. Area Under the Curve was 96.5% with brain region delineation of EOAD compared to LOAD. This study indicates parietal atrophy less than 30% of normal on clinical MRI scans is suggestive of EOAD compared to LOAD.
| S-EPMC10623969 | biostudies-literature
Project description:Comparative studies of colorectal cancer (CRC) according to the age of onset have found differences between early-onset CRC (EOCRC) and late-onset CRC (LOCRC). Using this as a starting point, we wished to determine whether intermediate-onset CRC (IOCRC) might also be considered as an independent group within CRC. We performed a retrospective comparative study of the clinicopathological and familial features, as well as of the symptoms and their duration, of a total of 272 subjects diagnosed with CRC classified into three groups according to the age-of-onset (98 EOCRC, 83 IOCRC and 91 LOCRC). The results show that from a clinicopathological point of view, IOCRC shared certain features with EOCRC (gender, prognosis), and with LOCRC (multiple primary CRCs), whereas it also had characteristics that were specific for IOCRC (mean number of associated polyps). A gradual progression was observed from EOCRC to LOCRC from a greater family aggregation to sporadic cases, in parallel with a change of Lynch Syndrome cases to the sporadic microsatellite instability pathway, with the IOCRC being a boundary group that is more related to EOCRC. With respect to symptoms, duration and correlation with stages, IOCRC appeared more similar to EOCRC. Clinically, IOCRC behaves as a transitional group between EOCRC and LOCRC, with features in common with both groups, but also with IOCRC-specific features. Excluding cases with familial cancer history, the awareness for EOCRC diagnosis should be extended to IOCRC.
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Project description:BackgroundThe impact of molecular aberrations on survival after resection of colorectal liver metastases (CLM) in patients with early-age-onset (EOCRC) versus late-age-onset colorectal cancer (LOCRC) is unknown.MethodsPatients who underwent liver resection for CLM with known RAS, BRAF and MSI status were retrospectively studied. The prognostic impact of RAS mutations by age was analysed with age as a categorical variable and a continuous variable.ResultsThe study included 573 patients, 192 with EOCRC and 381 with LOCRC. The younger the age of onset of CRC, the greater the negative impact on overall survival of RAS mutations in the LOCRC, EOCRC, and ≤40 years (hazard ratio (HR), 1.64 (95% confidence interval (CI), 1.23-2.20), 2.03 (95% CI, 1.30-3.17), and 2.97 (95% CI, 1.44-6.14), respectively. Age-specific mortality risk and linear regression analysis also demonstrated that RAS mutations had a greater impact on survival in EOCRC than in LOCRC (slope: -4.07, 95% CI -8.10 to 0.04, P = 0.047, R2 = 0.08).ConclusionAmong patients undergoing CLM resection, RAS mutations have a greater negative influence on survival in patients with EOCRC, more so in patients ≤40 years, than in patients with LOCRC and should be considered as a prognostic factor in multidisciplinary treatment planning.
| S-EPMC7884678 | biostudies-literature
Project description:Immune profiles of early onset vs late onset colorectal cancer
| PRJNA732397 | ENA
Project description:ObjectivesEarly- and late-onset Alzheimer's disease (EOAD and LOAD) share the same neuropathological traits but show distinct cognitive features. We aimed to explore baseline and longitudinal outcomes of global and domain-specific cognitive function in a well characterized cohort of patients with a biomarker-based diagnosis.MethodsIn this retrospective cohort study, 195 participants were included and classified according to their age, clinical status, and CSF AD biomarker profile: 89 EOAD, 37 LOAD, 46 young healthy controls (age ≤ 65 years), and 23 old healthy controls (>65 years). All subjects underwent clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture.ResultsWe found distinct neuropsychological profiles between EOAD and LOAD at the time of diagnosis. Both groups showed similar performances on memory and language domains, but the EOAD patients displayed worsened deficits in visual perception, praxis, and executive tasks (p < 0.05). Longitudinally, cognitive decline in EOAD was more pronounced than LOAD in the global outcomes at the expense of these non-amnestic domains. We found that years of education significantly influenced the decline in most of the neuropsychological tests. Besides, the APOE ε4 status showed a significant effect on the decline of memory-related tasks within the EOAD cohort (p < 0.05).InterpretationAge of onset is a main factor shaping the cognitive trajectories in AD patients, with younger age driving to a steeper decline of the non-memory domains. Years of education are related to a transversal decline in all cognitive domains and APOE ε4 status to a specific decline in memory performance in EOAD.
| S-EPMC9735361 | biostudies-literature
Project description:Early-onset (<50 years old) colorectal cancer (CRC) has been increasing worldwide and is associated with poor outcomes. Over 85% of the Saudi population are <50 years old, which put them at heightened risk of early-onset CRC. No study assessed the trends in CRC incidence rates among the Saudis. The Joinpoint Regression software by the Surveillance, Epidemiology, and End Results (SEER) program was used to estimate the magnitude and direction of CRC incidence trends by age and gender. The annual percentage change (APC) and the average annual percentage change (AAPC) between 2001 and 2016 were computed. In a sensitivity analysis, we also assessed trends using various age groups. Between 2001 and 2016, the early-onset CRC incidence (per 105) increased from 1.32 (95% CI: 1.11, 1.54) to 2.02 (95% CI: 1.83, 2.22) with AAPC (2.6, 95% CI: -0.4, 5.7). At same period, the late-onset incidence increased from 3.54 (95% CI: 3.10, 3.97) to 9.14 (95% CI: 8.62, 9.66) with AAPC (6.1, 95% CI: 3.5, 8.8). Among early-onset CRC patients, age 40-49 has the highest rates and women in this age group has higher rate than men. Our national data showed a gradual increase in CRC incidence rates, which reflect the global concern of early-onset CRC. Further research is needed to understand the etiology of early-onset CRC. Primary health care providers must be alerted about the increasing rate of early-onset CRC. To reduce the future burden of the disease, initiating CRC screening before age 50 is warranted.
| S-EPMC8460085 | biostudies-literature