Biomarker Identification via Spatial Transcriptomics Profiling of Colorectal Cancer and Colorectal Cancer with Liver Metastasis Stem Cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE271285 | GEO | 2025/06/26
REPOSITORIES: GEO
Similar Datasets
Project description:Purpose: This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC). Experimental Design: The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells especially in patients with distant metastasis was a prerequisite to select candidate genes. The mRNA expression of candidate gene was investigated by quantitative reversetranscription polymerase chain reaction (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study, and investigated the relationship between the expression and the clinicopathological feature in 274 CRC patients. Results: We identified 6 genes as candidates related to distant metastasis in CRC patients by microarray analysis. Among these genes, Osteoprotegerin (OPG) is known to have an association with aggressiveness in several cancers through inhibiting apoptosis by neutralizing the function of tumor necrosis factor related apoptosis inducing ligand (TRAIL). The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastasis than those without metastasis. The overexpression of OPG protein was significantly associated with worse overall survival and relapse free survival (RFS). Moreover, the overexpression of OPG protein was an independent risk factor for recurrence of CRC. Conclusion: The overexpression of OPG would be a predictive biomarker of recurrence and a target of the treatment for CRC. Total of 148 microarray datasets obtained from LCM and homogenized tissues of colorectal cancer patients were normalized using robust multi-array average (RMA) method under R 2.6.2 statistical software with affy package from BioConductor. Normalization was separately performed for LCM dataset and homogenized tissue dataset. The normalized gene expression levels were presented as log2-transformed values by RMA.
2011-02-28 | E-GEOD-21510 | biostudies-arrayexpress
Project description:The purpose of this study is to identify miRNAs involved in the pathology of colorectal cancer (CRC) liver metastasis and investigate their underlying mechanisms. A total of 39 miRNAs were identified to be differentially expressed between 16 primary CRC tissues with liver metastases and 16 CRC tissues without liver metastases from 32 patients by Affymetric miRNA microarrays. 16 coloretcal cancer tissues with liver metastasis and 16 colorectal cancer tissues without liver metastasis were included in this study for RNA extraction and hybridization on Affymetrix microarrays. We sought to identify the differentially expressed miRNAs between colorectal cancer tissues with and without liver metastasis.
2013-12-10 | E-GEOD-53159 | biostudies-arrayexpress
Project description:Distant metastasis is the major causes of death in colorectal cancer (CRC) patients. In order to identify genes influencing the prognosis of patients with CRC, we compared gene expression in primary tumors with and without distant metastasis using an oligonucleotide microarray. We also examined the expression of the candidate gene in 100 CRC patients by quantitative real-time reverse transcription PCR and studied the relationship between its expression and the prognosis of patients with CRC. As a result, we identified MUC12 as a candidate gene involved in metastasis processes by microarray analysis. Quantitative real-time reverse transcription PCR showed that MUC12 expression was significantly lower in cancer tissues than in adjacent normal tissues (P < 0.001). In stage II and stage III CRC, patients with low expression showed worse disease-free survival (P = 0.038). Multivariate analysis disclosed that MUC12 expression status was an independent prognostic factor in stage II and stage III CRC (relative risk, 9.532; 95% confidence interval, 2.303-41.905; P = 0.002). This study revealed the prognostic value of MUC12 expression in CRC patients. Moreover, our result suggests MUC12 expression is a possible candidate gene for assessing postoperative adjuvant therapy for CRC patients. Total of 111 microarray datasets (77 for LCM samples, and 17 pairs for homogenized samples from tumor and adjacent tissues) were normalized using robust multi-array average (RMA) method under R 2.6.2 statistical software together with BioConductor package, as described previously. Then, the gene expression levels were log2-transformed, and 62 control probe sets were removed for further analysis. In order to identify a set of genes associated with development of metastatic recurrence, we performed Wilcoxon rank-sum test for gene expression differences of 54,613 probe sets between recurrence and non-recurrence groups. Similarly, Wilcoxon singed-rank test was conducted to select genes which showed significant expression difference between tumor and adjacent tissue. Then, we selected a set of genes that satisfied both of above two criteria.
2010-03-05 | E-GEOD-18105 | biostudies-arrayexpress
Project description:To identify potential metastasis associated miRNAs in colorectal cancer (CRC), we performed miRNA array on normal mucosa, CRC tissues without metastasis and CRC tissues with distant metastasis.
2018-09-22 | GSE120300 | GEO
Project description:About 50% of colorectal cancer patients develop liver metastases. Patients with metastatic colorectal cancer have 5-year survival rates below 20% despite new therapeutic regimens. Tumor heterogeneity has been linked with poor clinical outcome, but was so far mainly studied via bulk genomic analyses. In this study we performed spatial proteomics via MALDI mass spectrometry imaging on six patient matched CRC primary tumor and liver metastases to characterize interpatient, intertumor and intratumor hetereogeneity. We found several peptide features that were enriched in vital tumor areas of primary tumors and liver metastasis and tentatively derived from tumor cell specific proteins such as annexin A4 and prelamin A/C. Liver metastases of colorectal cancer showed higher heterogeneity between patients than primary tumors while within patients both entities show similar intratumor heterogeneity sometimes organized in zonal pattern. Together our findings give new insights into the spatial proteomic heterogeneity of primary CRC and patient matched liver metastases.
2023-02-17 | PXD039409 | Pride
Project description:Colorectal cancer (CRC) is the third most common cancer worldwide and liver metastasis remains the major cause of death in CRC. Extensive genomic analysis provided valuable insight into the pathogenesis and progression of CRC. However, the major proteogenomic characterization of CRC liver metastasis is still unknown. We investigated proteogenomic characterization and performed comprehensive integrative genomic analysis of human colorectal cancer liver metastasis.
2019-12-27 | GSE93286 | GEO
Project description:Purpose: This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC). Experimental Design: The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells especially in patients with distant metastasis was a prerequisite to select candidate genes. The mRNA expression of candidate gene was investigated by quantitative reversetranscription polymerase chain reaction (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study, and investigated the relationship between the expression and the clinicopathological feature in 274 CRC patients. Results: We identified 6 genes as candidates related to distant metastasis in CRC patients by microarray analysis. Among these genes, Osteoprotegerin (OPG) is known to have an association with aggressiveness in several cancers through inhibiting apoptosis by neutralizing the function of tumor necrosis factor related apoptosis inducing ligand (TRAIL). The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastasis than those without metastasis. The overexpression of OPG protein was significantly associated with worse overall survival and relapse free survival (RFS). Moreover, the overexpression of OPG protein was an independent risk factor for recurrence of CRC. Conclusion: The overexpression of OPG would be a predictive biomarker of recurrence and a target of the treatment for CRC.
2011-02-28 | GSE21510 | GEO
Project description:Colon and liver have an inseparable relationship since embryological development. More than half of colorectal cancer patients developed liver metastases accompanied with poor prognosis. Recent evidence suggests that distant metastatic organs are “educated” by primary tumor-derived extracellular vesicles. Here we found that the liver-specific pro-metastatic effect of colorectal cancer (CRC)-derived small extracellular vesicles (sEVs). In vivo experiments showed that the injected fluorescence-labeled CRC-derived sEVs were accumulated and taken up by macrophages in the mouse liver. MicroRNA sequencing revealed the highest expression of microRNA (miR)-21-5p in CRC-derived sEVs. In vitro co-culture experiments showed that the sEVs polarized macrophages toward an interleukin-6(IL-6)-secreting type of macrophages. Further mouse experiments and microarray studies indicated that the CRC-sEVs increased macrophage invasion and induced an inflammatory microenvironment in the liver, which promoted liver metastasis of orthotropic- transplanted CRC cells. Most importantly, the TCGA data analysis and clinical sample examinations demonstrated that miR-21-5p expressions were sharply raised in the CRC tissues. We apply Tethered Cationic Lipoplex Nanoparticles (tCLN) technology in detecting CRC patients’ sEVs miR-21 in plasma and found strong correlation between sEVs-miR-21 and CRC liver metastasis. The serum IL-6 level was much higher in CRC patients with liver metastasis, and the liver metastasis relevance of MiR-21, macrophages, and IL-6 in CRC patients. Thus, we propose the role of CRC-derived sEVs in the formation of an inflammatory pre-metastatic niche in liver for CRC metastasis through macrophage polarization via a miR-21/TLRs pro-inflammation pathway.
2019-07-01 | GSE100435 | GEO
Project description:These samples are part of a study investigating cancer cell plasticity in colorectal cancer metastasis. Spatial transcriptomics was performed using 10x Genomics Visium on colorectal cancer liver metastatic patient samples.
2025-04-22 | E-MTAB-13655 | biostudies-arrayexpress