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ABSTRACT:
PROVIDER: PRJNA663646 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We attempted to screen and identify new plasma EV delivered microRNA can simultaneously diagnose AA, early CRC and advanced CRC in healthy people. We employed microRNA deep sequencing assay for the primary screen and performed TaqMan microRNA assay for further test and validation. Through stepwise screen and validation in two independent cohorts (cohort I: n=75, cohort II: n=104), we demonstrated that plasma EV-delivered miR-185-5p is a potential indicator of AA and CRC in Chinese patients. In the supplementary phase, we also preliminarily proved that miR-185-5p can promote the development of CRC in vivo and in vitro.
2023-09-11 | GSE220445 | GEO
Project description:Background: Colorectal cancer (CRC) is one of the major causes of cancer-related death worldwide. Although commercial biomarkers of CRC are currently available, they are still lacking in terms of sensitivity and specificity; thus, searching for reliable blood-based biomarkers are important for the primary screening of CRC. Methods: Plasma samples of patients with non-metastatic (NM) and metastatic (M) CRC and healthy controls were fractionated using MARS-14 immunoaffinity chromatography. The flow-through and elute fractions representing low- and high-abundant proteins, respectively, were analyzed by label-free quantitative proteomics mass spectrometry. The functional analysis of the proteins with greater than 1.5-fold differential expression level between the CRC and the healthy control groups were analyzed for their biological processes and molecular functions. In addition, the levels of plasma proteins showing large alterations in CRC patients were confirmed by immunoblotting using two independent cohorts. Moreover, receiver operating characteristic (ROC) curve analysis was performed for individual and combinations of biomarker candidates so as to evaluate the diagnostic performance of biomarker candidates. Results: From 163 refined identifications, five proteins were up-regulated and two proteins were down-regulated in NM-CRC while eight proteins were up-regulated and three proteins were down-regulated in M-CRC, respectively. Altered plasma proteins in NM-CRC were mainly involved in complement activation, while those in M-CRC were clustered in acute-phase response, complement activation, and inflammatory response. Results from the study- and validation-cohorts indicate that the levels of LRG, C9, AGP1, and A1AT were statistically increased, while FN level was statistically decreased in CRC patients compared to healthy controls, with most alterations found in a metastatic stage-dependent manner. ROC analysis revealed that FN exhibited the best diagnostic performance to discriminate CRC patients and healthy controls while AGP1 showed the best discrimination between the disease stages in both cohorts. The combined biomarker candidates, FN+A1AT+AGP1, exhibited perfect discriminatory power to discriminate between the CRC population and healthy controls whereas LRG+A1AT+AGP1 was likely to be the best panel to discriminate the metastatic stages in both cohorts. Conclusions: This study identified and quantified distinct plasma proteome profiles of CRC patients. Selected CRC biomarker candidates including FN, LRG, C9, A1AT, and AGP1 may be further applied for screening larger cohorts.
2023-03-29 | PXD040999 | Pride
Project description:In the majority of colorectal cancers (CRC) under clinical suspicion for a hereditary cause, the disease-causing genetic factors are still to be discovered. In order to identify such genetic factors we stringently selected a discovery cohort of 41 CRC index patients with microsatellite-stable tumors. All patients were below 40 years of age at diagnosis and/or exhibited an overt family history. We employed genome-wide copy number profiling using high-resolution SNP-based array CGH on germline DNA, which resulted in the identification of novel copy number variants (CNVs) in 6 patients (15%) encompassing, among others, the cadherin gene CDH18, the bone morphogenetic protein antagonist family gene GREM1, and the breakpoint cluster region gene BCR. In addition, two genomic deletions were encountered encompassing two microRNA genes, hsa-mir-491/KIAA1797 and hsa-mir-646/AK309218. None of these CNVs has previously been reported in relation to CRC predisposition in humans, nor were they encountered in large control cohorts (>1,600 unaffected individuals). Since several of these newly identified candidate genes may be functionally linked to CRC development, our results illustrate the potential of this approach for the identification of novel candidate genes involved in CRC predisposition. Copy number detection was performed using CNAG2.0 software for 250k SNP arrays and using the Affymetrix Genotyping Console v2.1 software for SNP 6.0 arrays, Reference genomes are included in this data set.
2010-11-01 | GSE13429 | GEO
Project description:Five-year overall survival of stage III colorectal cancer (CRC) patients treated with standard adjuvant chemotherapy (ACHT) is highly variable. Genomic biomarkers and/or transcriptomic profiles identified lack of adequate validation. Aim of our study was to identify and validate molecular biomarkers predictive of ACHT response in stage III CRC patients by a transcriptomic approach. From a series of CRC patients who received ACHT, two stage III extreme cohorts (unfavorable vs. favorable prognosis) were selected. RNA sequencing was performed from fresh frozen explants. Tumors were characterized for somatic mutations. Validation was performed in stage III CRC patients extracted from two GEO datasets. According to disease free survival (DFS), 108 differentially expressed genes (104/4 up/downregulated in the unfavorable prognosis group) were identified. Among 104 upregulated genes, 42 belonged to olfactory signaling pathways, 62 were classified as pseudogenes (n = 17), uncharacterized noncoding RNA (n = 10), immune response genes (n = 4), microRNA (n = 1), cancer-related genes (n = 14) and cancer-unrelated genes (n = 16). Three out of four down-regulated genes were cancer-related. Mutational status (i.e., RAS, BRAF, PIK3CA) did not differ among the cohorts. In the validation cohort, multivariate analysis showed high PNN and KCNQ1OT1 expression predictive of shorter DFS in ACHT treated patients (p = 0.018 and p = 0.014, respectively); no difference was observed in untreated patients. This is the first study that identifies by a transcriptomic approach and validates PNN and KCNQ1OT1 as molecular biomarkers predictive of chemotherapy response in stage III CRC patients. After a further validation in an independent cohort, PNN and KCNQ1OT1 evaluation could be proposed to prospectively identify stage III CRC patients benefiting from ACHT.
2020-05-03 | GSE122246 | GEO
Project description:In the majority of colorectal cancers (CRC) under clinical suspicion for a hereditary cause, the disease-causing genetic factors are still to be discovered. In order to identify such genetic factors we stringently selected a discovery cohort of 41 CRC index patients with microsatellite-stable tumors. All patients were below 40 years of age at diagnosis and/or exhibited an overt family history. We employed genome-wide copy number profiling using high-resolution SNP-based array CGH on germline DNA, which resulted in the identification of novel copy number variants (CNVs) in 6 patients (15%) encompassing, among others, the cadherin gene CDH18, the bone morphogenetic protein antagonist family gene GREM1, and the breakpoint cluster region gene BCR. In addition, two genomic deletions were encountered encompassing two microRNA genes, hsa-mir-491/KIAA1797 and hsa-mir-646/AK309218. None of these CNVs has previously been reported in relation to CRC predisposition in humans, nor were they encountered in large control cohorts (>1,600 unaffected individuals). Since several of these newly identified candidate genes may be functionally linked to CRC development, our results illustrate the potential of this approach for the identification of novel candidate genes involved in CRC predisposition. Copy number detection was performed using CNAG2.0 software for 250k SNP arrays and using the Affymetrix Genotyping Console v2.1 software for SNP 6.0 arrays, Reference genomes are included in this data set. Germline genomic DNA from 41 patients with early-onset microsatellite stable colorectal cancer was hybridized on Affymetrix Nsp/6.0 SNP-based arrays according to manufacturer's procedures.
2010-11-01 | E-GEOD-13429 | biostudies-arrayexpress
Project description:The objective of this study is to identify a gene set to predict recurrence of colorectal cancer (CRC) patients. We generated RNA-seq data of 110 primary CRC samples and identified significant genes associated with recurrence of CRC. Through diverse statistical methods including generalized linear model likelihood ratio test, significant 10 genes were identified. In the validation cohorts, a risk classifier consisting of the 10 genes was an independent risk factor in colorectal cancers.
2019-10-29 | GSE107422 | GEO
Project description:The objective of this study is to identify a prognostic signature in colorectal cancer (CRC) patients with diverse progression and heterogeneity of CRCs. We generated RNA-seq data of 54 samples (normal colon, primary CRC, and liver metastasis) from 18 CRC patients and, from the RNA-seq data, identified significant genes associated with aggressiveness of CRC. Through diverse statistical methods including generalized linear model likelihood ratio test, two significantly activated regulators were identified. In the validation cohorts, two activated regulators were independent risk factors and potential chemotherapy-sensitive agenets in colorectal cancers.
2014-08-31 | GSE50760 | GEO
Project description:A core task to understand the consequences of non-coding single nucleotide polymorphisms (SNP) is to identify their genotype specific binding of transcription factor (TF). Here, we generate a large-scale TF-SNP interaction map for a selection of 116 colorectal cancer (CRC) risk loci and validated TF binding to 10 putatively functional SNPs. Our data further revealed TF binding complexity adjacent to the 116 risk loci, adding an additional layer of understanding to regulatory networks associated with CRC relevant loci.
2017-02-23 | PXD004435 | Pride
Project description:A core task to understand the consequences of non-coding single nucleotide polymorphisms (SNP) is to identify their genotype specific binding of transcription factor (TF). Here, we generate a large-scale TF-SNP interaction map for a selection of 116 colorectal cancer (CRC) risk loci and validated TF binding to 10 putatively functional SNPs. Our data further revealed TF binding complexity adjacent to the 116 risk loci, adding an additional layer of understanding to regulatory networks associated with CRC relevant loci.
2017-03-30 | MSV000080810 | MassIVE
Project description:Background: Preeclampsia (PE) is a multi-systemic maternal syndrome with substantial maternal and fetal morbidity and mortality. Currently, there is no clinically viable non-invasive biomarker assay for early detection, thus limiting the effective prevention and therapeutic strategies for PE. Methods: We conducted a discovery-training-validation three-phase retrospective and prospective study with cross-platform and multicenter cohorts. The initial biomarkers were discovered and verified in tissue specimens by small RNA sequencing and qRT-PCR. A miRNA signature (miR2PE-score) was developed using the Firth’s bias-reduced logistic regression analysis, and subsequently validated in two independent multinational retrospective cohorts and two prospective plasma cohorts. Results: We initially identified five PE-associated differentially expressed miRNAs from miRNA sequencing data and subsequently validated two miRNAs (miR-196b-5p and miR-584-5p) as robust biomarkers by association analysis with clinical characteristics and qRT-PCR in tissue specimens in the discovery phase. Using the Firth’s bias-reduced logistic regression analysis, we developed the miR2PE-score for the early detection of PE. The miR2PE-score showed a high diagnostic performance with an area under the receiver operating characteristic curve (AUROC) of 0.920, 0.848, 0.864 and 0.812 in training, internal and two external validation cross-platform and multicenter cohorts, respectively. Finally, we demonstrated the non-invasive diagnostic performance of the miR2PE-score in two prospective plasma cohorts with AUROC of 0.933 and 0.787. Furthermore, the miR2PE-score revealed superior performance in non-invasive diagnosis compared with previously published miRNA biomarkers. Conclusions: We developed and validated a novel and robust blood-based miRNA signature, which may serve as a promising clinically applicable non-invasive tool for the early detection of PE.
2022-09-21 | GSE206988 | GEO