Liver metastases originating from 4 colorectal cancer patients (CRC-LM).
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ABSTRACT:
PROVIDER: PRJNA898968 | ENA |
REPOSITORIES: ENA
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Project description:Using liver metastases from 4 colorectal cancer patients (CRC-LM), we explored one receptor: EGFR whose signaling triggers cell proliferation and is exacerbated in many tumors.
2023-06-14 | GSE217414 | GEO
Project description:Advanced colorectal cancer (CRC), a leading cause of death worldwide, is often accompanied by the development of liver metastases (LM), as well as skeletal muscle (SkM) wasting, i.e. cachexia. Despite affecting the majority of CRC patients, cachexia remains understudied and uncured. Moreover, only a single model of LM associated with CRC has been developed for the study of cachexia. Here we examined differential gene expression of skeletal muscles deriving from subcutaneous and metastatic C26 tumor hosts. Tumor hosts displaying LM experienced exacerbated muscle wasting compared to tumor hosts without LM.
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Project description:Analysis of colorectal primary tumors (pTU) and liver metastases (LM) tissue samples from patients and identify corresponding gene expression signatures
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Project description:Patients with peritoneal metastases (PM) originating from colorectal carcinoma (CRC) are curatively treated by cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C (MMC). We aim to improve patient selection and personalize treatment for patients treated with HIPEC by predicting MMC sensitivity. MMC sensitivity was determined for 12 CRC cell lines using two separate assays. Thirty-seven genes related to the FA-BRCA pathway, ATM-ATR pathway and enzymatic activation of MMC were correlated on expression array platform to MMC sensitivity. Low sensitivity correlated with a decrease in BLM (p=0.01) and BRCA2 (p=0.02) on mRNA expression level. Both genes are part of the Fanconi Anaemia-BRCA (FA-BRCA) pathway and therefore, functionality of the FA-BRCA pathway in cell lines was determined using chromosomal breakage assay and Western Blot for key protein FANCD2. However, FA-BRCA pathway functionality showed no correlation to MMC sensitivity. BLM was further analysed by staining for the corresponding protein with immunohistochemistry (IHC) on both CRC cell lines and patient material. In cell lines, weak intensity staining by IHC correlated to high sensitivity (p=0.04) to MMC. High BLM protein expression was significantly correlated to a decreased survival in patients after CRS and HIPEC (p=0.04). We are the first to have found a possible predictive biomarker for PM with CRC.
2015-12-01 | GSE50494 | GEO
Project description:We established an in vivo model of organ-specific colorectal cancer metastasis and demonstrated that the CD110+ tumor initiating cells contribute for colorectal liver metastasis. To gain a deeper understanding of its metastatic capacity, we performed a genome-wide transcriptome analysis on the CD110+ tumor cells derived from primary colon xenografts and their matched liver metastases. Results provide important information of the responses of the CD110+ cells during the process of liver colonization. Total RNA obtained from the CD110+ cells sorted from primary colorectal tumors (CRC102-PT and CRC108-PT) compared to those from the corresponding liver metastases (CRC102-LM and CRC108-LM).
2015-01-01 | E-GEOD-64595 | biostudies-arrayexpress
Project description:Colorectal cancer (CRC) is the third most common and second most deadly cancer worldwide. Treatments for metastatic CRC (mCRC) are still largely based on toxic chemotherapy regimens, but important insights into tumor biology enabled the development of targeted cancer therapies. Here, we describe a proteogenomic analysis of CRC liver metastases (metastatic CRC, mCRC), an ideal setting to analyze therapeutic resistance which occurs in a short time frame. We selected liver metastases from two CRC patients on both of which we performed deep proteome profiling and WES and RNAseq-directed database searches, identifying 10 predicted muttaions, one of which was KRAS G12V. finding we generated targeted parallel reaction monitoring (PRM) assays using stable isotope labelled standard (SIS) peptides to quantify the actual concentration (fmol per µg of total protein) of the mutated and canonical (wildtype) protein variants for 8 different mutations. We demonstrate on a total of 8 tumor and 6 paired healthy tissue samples (7 and 6 out of these KRASG12V) that PRM allows quantifying the actual mutation rate on the protein level from as little 10 µg of total protein starting amount and within a single 1 hour nano-LC-MS/MS run.
2019-12-04 | PXD014222 | Pride
Project description:PURPOSE: We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). PATIENTS AND METHODS: We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) of the expressed genes between these two groups. To characterize the clinical relevance of two highly-ranked differentially expressed signature genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.035), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p < 0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p < 0.0001) and LEF1 overexpression (p < 0.05) as important prognostic markers, but not tumor grade or SPP1. CONCLUSION: Among signature genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis. cDNA microarrays from the Stanford Functional Genomics Facility were used to perform mRNA transcript profiling of 31 freshly-frozen primary colorectal cancer specimens, and compared to published profiles of 32 unmatched colorectal liver metastases and 12 normal liver specimens.
2011-03-22 | E-GEOD-22834 | biostudies-arrayexpress
Project description:Background & Aims: The metastatic process is complex and remains a major obstacle in the management of colorectal cancer (CRC). To gain a better insight into the biologic events driving the metastatic process we investigated genomic aberrations in a large cohort of matched CRC primaries and distant metastases from various sites. Methods: In total, 62 primary colorectal cancers, 62 matched normal specimens, and 68 matched metastases (from liver, lung, ovary, omentum, and distant lymph nodes) were analyzed by high resolution array comparative genomic hybridization (array CGH) for DNA copy number changes. Findings were validated using a publicly available dataset consisting of 21 primary tumors and matched liver metastases. Fluorescence in situ hybridization (FISH) was used to confirm some of the DNA copy number changes observed. Results: Overall patterns of DNA copy number aberrations were highly similar between primary tumors and their metastases, confirming clonality. Additional copy number aberrations in metastasis are rare and rather than recurrent they were sporadic for individual patients. The only recurrent differences between primary tumors and their metastases were two chromosomal regions, 6q21 and 8q24.21 encompassing the MYC oncogene, that coamplified in three metastases of two patients (3.2%). FISH analysis confirmed the high level co-amplification in the metastasis, which were not detected in their primary tumors. Conclusions: Primary CRC and their metastases show highly similar patterns of DNA copy number changes, additional copy number aberrations in metastasis are rare and recurrences exceptional. These observations are consistent with the hypothesis that the metastatic potential is predestined early in the development of the primary tumor. In total, 62 primary colorectal cancers, 62 matched normal specimens, and 68 matched metastases (liver, lung, ovarian, omentum and distant lymph nodes) were analyzed by high resolution array comparative genomic hybridization (array CGH).
2014-02-10 | E-GEOD-38479 | biostudies-arrayexpress
Project description:We present a novel approach for investigating transcriptomic differences between primary colorectal cancers (CRC) and distant CRC metastases, which may help to identify primaries at high risk for future dissemination and to inform the development of metastasis-targeted therapies. Eliminating tissue specificity of the “host” organs where tumors are located and adjusting for confounders such as exposure to chemotherapy and radiation, allows for an effective comparison of primary CRC and metastatic lesion transcriptomes at both the gene and pathway levels. Using this approach, our discovery-validation design identified that metastases are characterized by reduced epithelial-mesenchymal-transition (EMT) but increased MYC target and DNA repair pathway activities. The most significant gene-level expression differences between primaries and metastases were in FBN2 and MMP3, which showed over a 7-fold difference. In addition, we uncovered two distinct subtypes of CRC metastases that are characterized by either EMT-inflammatory or proliferative phenotypes, and demonstrated that none of the metastases examined were of consensus molecular subtype (CMS) 3 suggesting subtype exclusivity. Highlighting transcriptome differences between primary tumors and CRC metastases delineates pathways that may be activated in metastases and may assist in the development and/or selection of existing targeted treatment regimens for individuals with metastatic disease.
2019-05-18 | GSE131418 | GEO
Project description:Colorectal cancer (CRC) patients suffer from the second highest mortality among all cancer entities. In half of all CRC patients, colorectal cancer liver metastases (CRLM) can be observed. Metastatic colorectal cancer is associated with poor overall survival and limited treatment options. Even after successful surgical resection of the primary tumor, metachronous liver metastases occur in one out of eight cases. The only available curative intended treatment is hepatic resection, but metachronous CRLM frequently recur after approximately one year. In this study, we performed a proteome analysis of three recurrent liver metastases of a single CRC patient by mass spectrometry. Despite surgical resection of the primary CRC and adjuvant chemotherapy plus cetuximab treatment, the patient developed three metachronous CRLM which occurred consecutively after 9, 21 and 31 months. We identified a set of 1,132 proteins expressed in the three metachronous CRLM, of which 481 were differentially regulated, including 81 proteins that were associated with the extracellular matrix (ECM). 56 ECM associated proteins were identified as upregulated in the third metastasis, 26 (46%) of which were previously described as negative prognostic markers in CRC, including tenascin C, nidogen 1, fibulin1 and vinculin. These data may reflect an ascending trend of malignancy from the first to the third metachronous colorectal cancer liver metastasis. Additionally, the results indicate different ECM phenotypes for recurrent metachronous metastasis, associated with different grades of malignancy and highlights the importance of individual analysis of molecular features in different, consecutive metastatic events in a single patient.
2021-09-09 | PXD020109 | Pride