Clinical significance of gene signature generated from the grade of tumor budding in colorectal cancer
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ABSTRACT:
PROVIDER: PRJNA602458 | ENA |
REPOSITORIES: ENA
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Project description:Tumor budding is a definite prognostic marker, but does not always show favorable reproducibility. We developed a new molecular signature related to tumor budding levels, a microscopic finding of dedifferentiation, using RNA extracted from the whole tissue section and disclosed its relevance to a high recurrence risk using an inhouse dataset and independent public datasets.
2020-04-24 | GSE143985 | GEO
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Project description:The Dicer ribonuclease III (RNase III) enzymes process long double-stranded RNA (dsRNA) into the small interfering RNAs (siRNAs) that direct RNA interference. Here, we describe the structure and activity of a catalytically active fragment of Kluyveromyces polysporus Dcr1, which represents the noncanonical Dicers found in budding yeast. The crystal structure reveals a homodimer that resembles bacterial RNase III but includes a novel N-terminal domain and newly identified catalytic residues conserved throughout eukaryotic RNase III enzymes. Biochemical analyses show that Dcr1 dimers bind cooperatively along the dsRNA substrate and cleave at precise intervals based on the distance between consecutive active sites. Thus, unlike canonical Dicers, which successively remove siRNA duplexes from the dsRNA termini, Dcr1 initiates processing in the interior and works outward. The distinct mechanism of budding-yeast Dicers establishes a novel paradigm for natural protein-based molecular rulers and imparts substrate preferences with ramifications for biological function. High-throughput sequencing of small RNAs generated by in vitro processing of long dsRNA using Kluyveromyces polysporus Dicer
2011-05-11 | E-GEOD-29168 | biostudies-arrayexpress
Project description:The Dicer ribonuclease III (RNase III) enzymes process long double-stranded RNA (dsRNA) into the small interfering RNAs (siRNAs) that direct RNA interference. Here, we describe the structure and activity of a catalytically active fragment of Kluyveromyces polysporus Dcr1, which represents the noncanonical Dicers found in budding yeast. The crystal structure reveals a homodimer that resembles bacterial RNase III but includes a novel N-terminal domain and newly identified catalytic residues conserved throughout eukaryotic RNase III enzymes. Biochemical analyses show that Dcr1 dimers bind cooperatively along the dsRNA substrate and cleave at precise intervals based on the distance between consecutive active sites. Thus, unlike canonical Dicers, which successively remove siRNA duplexes from the dsRNA termini, Dcr1 initiates processing in the interior and works outward. The distinct mechanism of budding-yeast Dicers establishes a novel paradigm for natural protein-based molecular rulers and imparts substrate preferences with ramifications for biological function.
2011-05-11 | GSE29168 | GEO
Project description:Background: SPOCK2 is a member of the SPOCK family, a 424-amino acid protein that binds to glycosaminoglycans to form proteoglycans. The purpose of this study was to explore expression profile of SPOCK2, and evaluate prognostic potential and its correlation with immune infiltration in high-grade serous ovarian cancer (HGSOC). Methods: Expression of SPOCK2 mRNA and protein between normal and tumor tissues were analyzed using the Cancer Genome Atlas database (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and the Human Protein Atlas (HPA) databases. Receiver operating characteristic (ROC) curve was used to evaluate diagnostic performance of SPOCK2. Kaplan-Meier method and Cox regression analysis were conducted to assess the effect of SPOCK2 on survival. Nomogram was used to predict the impact of SPOCK2 on prognosis. LinkedOmics were used to find correlated genes and perform functional enrichment analyses. The relationships between SPOCK2 and tumor infiltrating lymphocytes (TILs) were determined by tumor-immune system interaction database (TISIDB) and GSVA package (V1.34.0). Results: SPOCK2 was highly expressed in HGSOC tissue compared to normal tissue at both mRNA (p < 0.001) and protein (p = 0.03) levels. The area under the curve (AUC) is 0.894 (CI: 0.865-0.923). Kaplan-Meier analysis showed that HGSOC patients with high-level SPOCK2 mRNA expression had a worse overall survival (OS) than those with a low expression (HR = 1.45, p = 0.005). Univariate logistic regression analysis found that age, primary therapy outcome, tumor status, tumor residual, and SPOCK2 expression level were significantly associated with OS (p < 0.05). The nomogram model indicated an effective predictive performance of SPOCK2. Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) term analyses showed that SPOCK2 were mainly involved in regulating extracellular matrix. Immune infiltration analysis showed that SPOCK2 may correlate with abundance of TILs. Conclusion: SPOCK2 has potentials to estimate diagnosis and prognosis for HGSOC and is involved in regulating extracellular matrix and immune cell infiltration.
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Project description:This study investigates the ability of tumor budding to identify prognosis in different MMR states and different levels of tumor lymphocyte infiltration. Tumor budding is usually defined as an isolated single cancer cell or a cluster of up to four cancer cells located at the front of an infiltrating tumor.
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Project description:Tumor budding (TB) has become a crucial factor for predicting the malignancy grade and prognostic outcome for multiple solid cancers.Studies have investigated the prognostic value of TB within hepatocellular carcinoma (HCC). However, its molecular mechanism within HCC remains unclear. This is the first study to discover and compare the expression of differentially expressed genes (DEGs) between TB-positive and TB-negative HCC tissues. Total RNA was extracted from 40 fresh HCC tissue samples with different TB statuses and then sequenced. This study provides insights into the possible mechanisms of TB in HCC and revealed potential predictive diagnosis markers and treatment targets for HCC.
2023-04-02 | GSE227335 | GEO