RNA Sequencing of Colorectal Liver Metastases
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ABSTRACT:
PROVIDER: EGAS00001002945 | EGA |
REPOSITORIES: EGA
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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
Project description:Dissemination of primary tumors to distant anatomical sites has a substantial negative impact on patient prognosis. The liver is a common site for metastases from colorectal cancer, and patients with hepatic metastases have generally much shorter survival, raising a need to develop and implement novel strategies for targeting metastatic disease. The extracellular matrix (ECM) is a meshwork of highly crosslinked, insoluble, high molecular weight proteins maintaining tissue integrity and establishing cell-cell interactions. Emerging evidence identifies the importance of the ECM in cancer cell migration, invasion, intravasation, and metastasis. Here, we isolated the extracellular matrix from MC38 mouse liver metastases using our optimized method of mild detergent solubilization followed by biochemical enrichment. The matrices were subjected to label-free quantitative mass spectrometry analysis, revealing proteins highly abundant in the metastatic matrisome. The resulting list of differentially expressed proteins significantly predicted survival in patients with colorectal cancer but not other cancers with strong involvement of the extracellular matrix component. One of the proteins upregulated in liver metastatic ECM, Annexin A1, was not previously studied in the context of cancer-associated matrisome. Here we show that Annexin A1 was markedly upregulated in colon cancer cell lines compared to cancer cells of other origin, and also overrepresented in human primary colorectal lesions as well as hepatic metastases in comparison with their adjacent healthy tissue counterparts. In conclusion, our study provides a comprehensive ECM characterization of MC38 experimental liver metastases and proposes Annexin A1 as a putative target for this disease.
2020-05-26 | PXD013350 | Pride
Project description:Almost half of all patients diagnosed with colorectal cancer develop liver metastases. The potential role of intra-individual metastatic heterogeneity remains poorly characterized. By high-resolution DNA copy number analyses and a novel approach based on pair-wise genetic distance, we examined the genetic heterogeneity among multiple liver metastatic deposits obtained from 45 patients subject to curative liver resection. We found large variation in intra-individual metastatic heterogeneity. A high level of heterogeneity was associated with poor patient survival. Patients with metachronous metastases who received chemotherapy had significantly more heterogeneity than chemonaïve patients.
2016-07-11 | GSE63490 | GEO
Project description:In this study we aimed to explore the molecular landscape of hepatic metastases and adjacent tissue in order to delineate a potential molecular signature that may be predictive for clinical benefit of CRCLM resection. Consecutive patients who underwent CRCLM resection between 2008 and 2015 at RMC, and for whom pathological specimen was available were included in the study. Cases were divided into two cohorts based on the interval between resection of liver metastases and disease recurrence- patients with less than 12-month interval were defined as ×´poor prognosis×´ (PP) and patients with more than 12 months as ×´good prognosis×´ (GP). Clinical data was retrieved from the medical records. Proteomic analysis was performed on the pathological bio specimen and correlated to demographics and clinical outcomes. Fifty-eight patients were included in the study. 29 in the GP cohort and 29 in the PP cohort. Proteomic analysis of the two-cohort revealed 99 proteins that were 38 differentially expressed, about a third of them associate with the extracellular matrix (ECM) pathways as the matrix metalloproteinases (MMPs).
2022-02-16 | PXD022613 | Pride
Project description:Comparison of genomic alterations of primary colorectal cancers with liver metastases of the same patient Keywords: array CGH, colorectal cancer, colon cancer, liver metastasis 21 primary colorectal cancers and 21 matched liver metastases hybridized against sex-matched control pools
2010-07-07 | E-GEOD-10179 | biostudies-arrayexpress
Project description:Eicosapentaenoic acid in its free fatty acid form (EPA-FFA), 2g daily, is safe and well-tolerated in patients undergoing liver resection surgery for colorectal liver metastasis.Oral EPA incorporates into colorectal liver metastasis tissue. EPA-FFA treatment is associated with reduced vascularity of liver metastases in ω-3 PUFA-naïve patients. Preoperative (median 30 days) EPA-FFA treatment may have prolonged benefit on postoperative overall and disease-free survival. We used whole genome expression array to study whether systemic CCL2 level changes were linked to a specific tumour gene expression profile in colorectal liver metastasis patients treated with EPA-FFA.
2016-03-16 | GSE79266 | GEO
Project description:To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment. 57 samples of patients with stage IV colorectal cancer. We compared using Affymetrix chips gene expression profiles between primary tumors and hepatic metastases
2013-09-01 | E-GEOD-49355 | biostudies-arrayexpress
Project description:To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment. 57 samples of patients with stage IV colorectal cancer. We compared using Affymetrix chips gene expression profiles between primary tumors and hepatic metastases
2014-10-15 | E-GEOD-62321 | biostudies-arrayexpress
Project description:Comparison of expression profiles of primary colorectal cancers with liver metastases of the same patient. Additionally, expression data of normal colon and liver tissue. Abstract of publication will be included upon publication Keywords: expression profiling, colorectal cancer, colon cancer, liver metastasis, normal colonic tissue, normal liver tissue RNA of 18 primary colorectal cancers, 18 matched liver metastases, 7 normal colon epithelium samples and 5 normal liver tissue samples hybridized on Human Sentrix-6 V2 (Illumina)
2010-07-07 | E-GEOD-14297 | biostudies-arrayexpress
Project description:mRNA sequencing by Lexogen Quantseq 3 prime of colorectal liver metastases
| PRJEB35154 | ENA