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Early onset lone atrial fibrillation case-control study

ABSTRACT: Target sequencing W/ TruSight Cardio Sequencing Kit. 395 early onset lone AF cases and 375 controls. Sequencing was performed on Illumina NextSeq and HiSeq 2500 systems.395 early.

PROVIDER: EGAS00001003208 | EGA |

REPOSITORIES: EGA

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0c230add-0799-4335-930d-c21079df3a1e - samples

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Project description:A technical comparison of Agilent SureSelect Focussed Exome and TruSight One Mendeliome sequencing kits, by triplicate sequencing of the cell line DNA of NA12878, NA12891, NA12892 and NIST RM8395

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Early onset colorectal cancer tissues and late onset colorectal cancer tissues

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.

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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.

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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.

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