Early onset and average onset colorectal cancer with matched normal colon tissues
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE281413 | GEO | 2025/12/01
REPOSITORIES: GEO
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Project description:Early onset and average onset colorectal cancer with matched normal colon tissues
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Project description:Placental Immune alterations in early-onset preeclampsia and late-onset preeclampsia
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Project description:Contrarily to late-onset (LO) colorectal cancer (CRC), early-onset (EO) CRC incidence is increasingly growing. Several factors, such as obesity, chronic inflammation, and intestinal dysbiosis, can increase the general risk of CRC. However, little is known about the biology of EO-CRC. To evaluate whether such selective rise in the incidence of EO-CRC patients mirrors a distinct transcriptomic profile, the investigators will first dissect EO-CRC’s transcriptomic landscape.
Then, the investigators will investigate the colorectal cancer stem cell (CSC) compartment by in vitro functional assays and RNA-seq analysis. Because our preliminary data indicate an increased aggressiveness of the tumor microenvironment (TME) in EO-CRC,the investigators propose to investigate the CSC niche and the interaction with the TME to dissect the molecular and cellular pathways occurring in EO-CRC.
A cohort of 30 EO-CRC patients (<50 years old) will be enrolled and fully characterized. About 10 EO-CRC-derived CSCs in the form of organoids and spheroids will be generated. Since the relevant differences between CR-CSCs isolated from EO-CRC vs LO-CRC patients are still unknown, the investigators will gain information about their specific features such as clonogenic activity, tumorigenic/invasive capacity, and about differences in the mechanisms regulating their cross-talk with TME components.
| 64348 | ecrin-mdr-crc
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:Preeclampsia is a severe placenta-related pregnancy disorder that is generally divided into two subtypes named early-onset preeclampsia (onset <34 weeks of gestation), and lateonset preeclampsia (onset ≥34 weeks of gestation), with distinct pathophysiological origins. Both forms of preeclampsia have been associated with maternal systemic inflammation. However, alterations in the placental immune system have been less well characterized. Here, we studied immunological alterations in early- and late-onset preeclampsia placentas using a targeted expression profile approach. RNA was extracted from snap-frozen placenta samples (healthy n=13, early-onset preeclampsia n=13, and late-onset preeclampsia n=6). The expression of 730 immune-related genes from the Pan Cancer Immune Profiling Panel was measured, and the data were analyzed Q10 in the advanced analysis module of nSolver software (NanoString Technology). The results showed that early-onset preeclampsia placentas displayed reduced expression of complement, and toll-like receptor (TLR) associated genes, specifically TLR1 and TLR4. Mast cells and M2 macrophages were also decreased in early-onset preeclampsia compared to healthy pl acentas. The findings were confirmed by an immunohistochemistry approach using 20 healthy, 19 early-onset preeclampsia, and 10 late-onset preeclampsia placentas. We conclude that the placental innate immune system is altered in early-onset preeclampsia compared to uncomplicated pregnancies. The absence of these alterations in late-onset preeclampsia placentas indicates dissimilar immunological profiles. The study revealed distinct pathophysiological processes in earlyonset and late-onset preeclampsia placentas and imply that a tailored treatment to each subtype is desirable.
2021-12-13 | GSE190639 | GEO
Project description:Epigenetic mechanisms such as DNA methylation are important regulators of gene expression and are frequently dysregulated early in breast carcinogenesis. The relationship between DNA methylation aberrations in normal breast tissue and breast cancer risk remains unclear. Disease-free breast tissue cores donated by high-risk (Tyrer-Cuzick lifetime risk ≥20%) and 78 average-risk women were obtained from the Susan G. Komen Tissue Bank and processed for whole methylome and whole transcriptome profiling. We identified 1355 CpGs that were differentially methylated between high- and average-risk breast tissues (ΔZ>0.5, FDR<0.05). Hypomethylated CpGs were overrepresented in high-risk tissue and were found predominantly (68%) in non-coding regions. Hypermethylated CpG sites were found equally in the gene body and non-coding regions. Transcriptomic analysis identified 67 differentially expressed genes (fold change≥2, FDR<0.05, 17 down 50 up), involved in chemokines signaling, metabolism and estrogen biosynthesis. Methylation-expression correlations revealed 6 epigenetically regulated genes in high-risk breast. This is the first gene expression/DNA methylation analysis of normal breasts from women at either high or average risk of breast cancer. Our discovery of epigenetically regulated genes associated with breast cancer risk using a unique resource of normal breast samples opens the doors to a deeper understanding of the process of cancer initiation and provides an opportunity to mechanistically dissect breast cancer susceptibility and risk-associated molecular alterations.
2021-09-30 | GSE164641 | GEO
Project description:Epigenetic mechanisms such as DNA methylation are important regulators of gene expression and are frequently dysregulated early in breast carcinogenesis. The relationship between DNA methylation aberrations in normal breast tissue and breast cancer risk remains unclear. Disease-free breast tissue cores donated by high-risk (Tyrer-Cuzick lifetime risk ≥20%) and 78 average-risk women were obtained from the Susan G. Komen Tissue Bank and processed for whole methylome and whole transcriptome profiling. We identified 1355 CpGs that were differentially methylated between high- and average-risk breast tissues (ΔZ>0.5, FDR<0.05). Hypomethylated CpGs were overrepresented in high-risk tissue and were found predominantly (68%) in non-coding regions. Hypermethylated CpG sites were found equally in the gene body and non-coding regions. Transcriptomic analysis identified 67 differentially expressed genes (fold change≥2, FDR<0.05, 17 down 50 up), involved in chemokines signaling, metabolism and estrogen biosynthesis. Methylation-expression correlations revealed 6 epigenetically regulated genes in high-risk breast. This is the first gene expression/DNA methylation analysis of normal breasts from women at either high or average risk of breast cancer. Our discovery of epigenetically regulated genes associated with breast cancer risk using a unique resource of normal breast samples opens the doors to a deeper understanding of the process of cancer initiation and provides an opportunity to mechanistically dissect breast cancer susceptibility and risk-associated molecular alterations.
2021-09-30 | GSE164640 | GEO
Project description:The incidence of sporadic early-onset colon cancer (EOCC) has increased worldwide. The molecular mechanisms in the tumor and the tumor microenvironment in EOCC are not fully understood. The aim of this study is to unravel unique spatial transcriptomic and proteomic profiles in tumor epithelial cells and cancer-associated fibroblasts (CAFs). Sporadic colon cancer FFPE tissue samples were divided into patients diagnosed with EOCC (<50 yrs) and late-onset colon cancer (LOCC, ≥50 yrs). Spatial transcriptomic analysis of 112 areas of interest (AOIs) were performed using Nanostring GeoMx digital spatial profiling. The data generated was combined with in silico analysis and functional assays to characterize FAP(+) CAFs at the EOCC tumor invasive margin.
2023-11-22 | GSE240531 | GEO
Project description:We sequenced mRNA from four biological replicates of each tissue before (T1) and after the onset of maturation (T2, T3, T4). A total of 3.2 billion paired-end reads were mapped against the Atlantic salmon reference genome with 72% mapping efficiency to create an average depth of 50 million reads per library. The number of differentially expressed genes (DEGs) increased with elapsed time following the onset of the long light photoperiod for the two BPG axis tissues (pituitary and ovary). Of these, the ovary underwent the most dramatic remodelling over time with 403, 1,709 and then 3,497 DEGs observed at timepoints T2, T3 and T4 respectively. This increasing trajectory of differential ngene expression, coupled with the elevated GSI following the light stimuli, strongly suggests the experimental approach successfully initiated the onset of maturation. Next, we identified clusters of DEGs in each of the analysed tissues, which describe their physiological roles. The identity of the DEGs, in response to the onset of maturation, revealed the key players involved in the earliest triggers into maturation. Among these, upregulation of genes encoding specififc pituitary hormones such as gonadotropins along with genes encoding transcription factors (such as GATA2) are significant in controlling onset of maturation. In addition, genes encoding pituitary hormone receptors and follicular development were upregulated in ovary.
2020-08-28 | GSE157001 | GEO