Immune gene signatures in human colorectal tumors with different GSNOR/ADH5 expression
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE227372 | GEO | 2023/03/17
REPOSITORIES: GEO
Similar Datasets
Project description:Immune gene signatures in human colorectal tumors with different GSNOR/ADH5 expression
| PRJNA945046 | ENA
Project description:ADH5 encodes for the protein GSNOR, an alchol dehydrogenase acting as a denitrosylase. GSNOR reduces S-nitrosoglutathione (GSNO) to an unstable intermediate, S-hydroxylaminoglutathione, which then rearranges to form glutathione sulfonamide, or in the presence of GSH, forms oxidized glutathione (GSSG) and hydroxylamine
2022-12-21 | GSE211114 | GEO
Project description:Colorectal cancer (CRC) is the third most diagnosed type of cancer and the second leading cause of cancer death worldwide. Despite the increasing knowledge of CRC molecular biology and the development of new targeted therapies, its high heterogeneity hampers the efficacy of current treatments. Thus, there is a pressing need to identify new effective therapeutic targets and improve immune therapies for these patients. In this regard, S-nitrosoglutathione reductase (GSNOR) is a denitrosylase enzyme that has been suggested to play a tumour suppressor role, although the mechanisms responsible are still largely unclear. Therefore, the main objective of this project was to understand the role of GSNOR in CRC tumorigenesis and its therapeutic implications. Firstly, we classified CRC tumours as GSNOR-high or low according to their GSNOR expression as assessed by immunohistochemistry (IHC). Accordingly, we found that GSNOR deficiency was associated with worse prognosis factors such as a larger tumour size at diagnosis, higher TNM stage, higher grade of tumour budding (TB), the CMS4 subtype, lower expression of the intestinal differentiation markers CDX2 and AE1/AE3 cytokeratin and a worse progression free survival (PFS) and overall survival (OS). We next investigated the differences in gene expression between CRC GSNOR-high and low tumours, uncovering significant alterations in metabolism and immune system pathways. Hence, GSNOR-deficient tumours were characterized by immune suppressive features and a dysregulation of their metabolism, favouring other metabolic pathways than OXPHOS.
2024-04-13 | GSE263844 | GEO
Project description:Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of numerous types of cancer, including colorectal cancer (CRC). Patients with CRC and deficient mismatch repair or high microsatellite instability could benefit from ICI treatment, although the response rate of most patients is low. Therefore, the immune subtyping of patients with CRC is required in order to determine the subtypes suitable for ICI treatment. The present study used a cohort of patients with CRC from The Cancer Genome Atlas (TCGA) to perform molecular subtyping, with results validated in three CRC cohorts from the Gene Expression Omnibus. Non-negative matrix factorization was used to achieve consensus molecular subtyping. The tumor immune dysfunction and exclusion algorithm was used to predict potential ICI therapy responses and gene set enrichment analysis was performed to define different pathways associated with the immune response. Two distinct subtypes of CRC were finally identified in TCGA cohorts, which were characterized as significantly different prognostic subtypes (low-risk and high-risk subtypes). Higher expression of programmed death-ligand 1, higher proportion of tumor-infiltrating lymphocytes and tumor mutation burden were significantly enriched in the low-risk subtype. Further pathway analysis revealed that the low-risk subtype was associated with immune response activation and signaling pathways involved in 'antigen processing and presentation'. Three independent CRC cohorts were used to validate the above findings. In summary, two clinical CRC subtypes were identified, which are characterized by significantly different survival outcomes and immune infiltration patterns. The findings of the present study suggest that ICI treatment may be more effective in the low-risk CRC subtype.
| S-EPMC7285802 | biostudies-literature
Project description:Age-related obesity is a growing public health concern linked to various metabolic disorders, yet its underlying mechanisms remain incompletely understood. Here we report that S-nitrosoglutathione reductase (GSNOR), a pivotal denitrosation enzyme, increases in adipose tissue of both male mice and humans from middle-age. GSNOR knockout protects against age-related weight gain and enhances metabolism, whereas adipose-specific GSNOR knock-in mice promotes obesity and metabolic decline. Further investigation reveals that aged GSNOR KO mice maintain higher mitochondrial content and more beige adipocytes, whereas adipose-specific GSNOR overexpression promotes adipose tissue whitening. Mechanistically, GSNOR denitrosates Beclin-1 at cysteine 351 and mutation of this site (Beclin-1C351A) increases autophagy by enhancing Beclin-1 and ATG14 interaction, thereby accelerating beige-to-white adipocyte conversion. Together, our findings reveal that GSNOR regulates adipose tissue remodeling during aging through Beclin-1 S-nitrosation, pointing to a potential therapeutic target for age-related obesity.
2026-01-26 | GSE317377 | GEO
Project description:BackgroundColorectal cancer (CRC) is a significant health issue, with notable incidence rates in Norway. The immune response plays a dual role in CRC, offering both protective effects and promoting tumor growth. This research aims to provide a detailed screening of immune-related genes and identify specific genes in CRC and adenomatous polyps within the Norwegian population, potentially serving as detection biomarkers.MethodsThe study involved 69 patients (228 biopsies) undergoing colonoscopy, divided into CRC, adenomatous polyps, and control groups. We examined the expression of 579 immune genes through nCounter analysis emphasizing differential expression in tumor versus adjacent non-tumorous tissue and performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) across patient categories.ResultsKey findings include the elevated expression of CXCL1, CXCL2, IL1B, IL6, CXCL8 (IL8), PTGS2, and SPP1 in CRC tissues. Additionally, CXCL1, CXCL2, IL6, CXCL8, and PTGS2 showed significant expression changes in adenomatous polyps, suggesting their early involvement in carcinogenesis.ConclusionsThis study uncovers a distinctive immunological signature in colorectal neoplasia among Norwegians, highlighting CXCL1, CXCL2, IL1B, IL6, CXCL8, PTGS2, and SPP1 as potential CRC biomarkers. These findings warrant further research to confirm their role and explore their utility in non-invasive screening strategies.
| S-EPMC11229009 | biostudies-literature
Project description:The immune system is crucial in regulating colorectal cancer (CRC) tumorigenesis. Identification of immune-related transcriptomic signatures derived from the peripheral blood of patients with CRC would provide insights into CRC pathogenesis, and suggest novel clues to potential immunotherapy strategies for the disease. The present study collected blood samples from 59 patients with CRC and 62 healthy control patients and performed whole blood gene expression profiling using microarray hybridization. Immune-related gene expression signatures for CRC were identified from immune gene datasets, and an algorithmic predictive model was constructed for distinguishing CRC from controls. Model performance was characterized using an area under the receiver operating characteristic curve (ROC AUC). Functional categories for CRC-specific gene expression signatures were determined using gene set enrichment analyses. A Kaplan-Meier plotter survival analysis was also performed for CRC-specific immune genes in order to characterize the association between gene expression and CRC prognosis. The present study identified five CRC-specific immune genes [protein phosphatase 3 regulatory subunit Bα (PPP3R1), amyloid β precursor protein, cathepsin H, proteasome activator subunit 4 and DEAD-Box Helicase 3 X-Linked]. A predictive model based on this five-gene panel showed good discriminatory power (independent test set sensitivity, 83.3%; specificity, 94.7%, accuracy, 89.2%; ROC AUC, 0.96). The candidate genes were involved in pathways associated with 'adaptive immune responses', 'innate immune responses' and 'cytokine signaling'. The survival analysis found that a high level of PPP3R1 expression was associated with a poor CRC prognosis. The present study identified five CRC-specific immune genes that were potential diagnostic biomarkers for CRC. The biological function analysis indicated a close association between CRC pathogenesis and the immune system, and may reveal more information about the immunogenic and pathogenic mechanisms driving CRC in the future. Overall, the association between PPP3R1 expression and survival of patients with CRC revealed potential new targets for CRC immunotherapy.
| S-EPMC8157333 | biostudies-literature
Project description:AbstractBurkitt lymphoma (BL) is characterized by a tumor microenvironment (TME) in which macrophages represent the main component, determining a distinct histological appearance known as "starry sky" pattern. However, in some instances, BL may exhibit a granulomatous reaction that has been previously linked to favorable prognosis and spontaneous regression. The aim of our study was to deeply characterize the immune landscape of 7 cases of Epstein-Barr virus-positive (EBV+) BL with granulomatous reaction compared with 8 cases of EBV+ BL and 8 EBV-negative (EBV-) BL, both with typical starry sky pattern, by Gene expression profiling performed on the NanoString nCounter platform. Subsequently, the data were validated using multiplex and combined immunostaining. Based on unsupervised clustering of differentially expressed genes, BL samples formed 3 distinct clusters differentially enriched in BL with a diffuse granulomatous reaction (cluster 1), EBV+ BL with typical starry sky pattern (cluster 2), EBV- BL with typical "starry sky" (cluster 3). We observed variations in the immune response signature among BL with granulomatous reaction and BL with typical "starry sky," both EBV+ and EBV-. The TME signature in BL with diffuse granulomatous reaction showed a proinflammatory response, whereas BLs with "starry sky" were characterized by upregulation of M2 polarization and protumor response. Moreover, the analysis of additional signatures revealed an upregulation of the dark zone signature and epigenetic signature in BL with a typical starry sky. Tumor-associated macrophages and epigenetic regulators may be promising targets for additional therapies for BL lymphoma, opening novel immunotherapeutic strategies.
| S-EPMC11372814 | biostudies-literature
Project description:BackgroundTumor-infiltrating leukocytes can either limit cancer growth or facilitate its spread. Diagnostic strategies that comprehensively assess the functional complexity of tumor immune infiltrates could have wide-reaching clinical value. In previous work we identified distinct immune gene signatures in breast tumors that reflect the relative abundance of infiltrating immune cells and exhibited significant associations with patient outcomes. Here we hypothesized that immune gene signatures agnostic to tumor type can be identified by de novo discovery of gene clusters enriched for immunological functions and possessing internal correlation structure conserved across solid tumors from different anatomic sites.MethodsWe assembled microarray expression datasets encompassing 5,295 tumors of the breast, colon, lung, ovarian and prostate. Unsupervised clustering methods were used to determine number and composition of gene clusters within each dataset. Immune-enriched gene clusters (signatures) identified by gene ontology enrichment were analyzed for internal correlation structure and conservation across tumors then compared against expression profiles of: 1) flow-sorted leukocytes from peripheral blood and 2) >300 cancer cell lines from solid and hematologic cancers. Cox regression analysis was used to identify signatures with significant associations with clinical outcome.ResultsWe identified nine distinct immune-enriched gene signatures conserved across all five tumor types. The signatures differentiated specific leukocyte lineages with moderate discernment overall, and naturally organized into six discrete groups indicative of admixed lineages. Moreover, seven of the signatures exhibit minimal and uncorrelated expression in cancer cell lines, suggesting that these signatures derive predominantly from infiltrating immune cells. All nine immune signatures achieved statistically significant associations with patient prognosis (p<0.05) in one or more tumor types with greatest significance observed in breast and skin cancers. Several signatures indicative of myeloid lineages exhibited poor outcome associations that were most apparent in brain and colon cancers.ConclusionsThese findings suggest that tumor infiltrating immune cells can be differentiated by immune-specific gene expression patterns that quantify the relative abundance of multiple immune infiltrates across a range of solid tumor types. That these markers of immune involvement are significantly associated with patient prognosis in diverse cancers suggests their clinical utility as pan-cancer markers of tumor behavior and immune responsiveness.
| S-EPMC5118876 | biostudies-literature
Project description:Nitric oxide (NO) is a signaling molecule that participates in diverse developmental processes in plants, and in responses to abiotic and biotic stresses. The main mode of action of NO is protein S-nitrosylation, the post-translational modification of thiol residues. S-nitrosoglutathione (GSNO) as a biological NO donor has a very important function in NO signaling since it can transfer its NO moiety to other proteins. The breakdown of GSNO and thus the level of S-nitrosylated proteins are regulated by GSNO-reductase (GSNOR). Arabidopsis knock out gsnor mutants have a pleotropic phenotype with a developmentally differences and impaired responses to biotic and abiotic stresses. Therefore, the main aim of the experiment was to identify genes involving in NO signaling by comparing WT and gsnor mutant.
2017-04-30 | E-MTAB-4756 | biostudies-arrayexpress