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.
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.
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
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.
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
Project description:In this study, we conducted a microarray-based analysis to identify differentially expressed miRNAs in CRC by comparing miRNA profiles among primary CRC tissues from patients with liver metastases, primary tissues without liver metastases, and liver metastatic lesions. microRNAs (miRNAs) have been shown to have a potential for cancer diagnosis lately. The main objective of this study is to identify a novel biomarker serum miRNA from the patients with colorectal cancer (CRC). Microarray analysis of miRNA expression was performed using paired pre- and post- operative serum from 10 CRC patients. Two miRNAs (let-7a, miR-199a-3p) decreased significantly in the post-operative serum when compared to pre-operative serum (P=0.015 and 0.029, respectively). Microarrays were performed for the testing cohort of primary CRC lesions (n=28) and liver metastatic lesions (n=8).
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.
Project description:In this study, we conducted a microarray-based analysis to identify differentially expressed miRNAs in CRC by comparing miRNA profiles among primary CRC tissues from patients with liver metastases, primary tissues without liver metastases, and liver metastatic lesions. microRNAs (miRNAs) have been shown to have a potential for cancer diagnosis lately. The main objective of this study is to identify a novel biomarker serum miRNA from the patients with colorectal cancer (CRC). Microarray analysis of miRNA expression was performed using paired pre- and post- operative serum from 10 CRC patients. Two miRNAs (let-7a, miR-199a-3p) decreased significantly in the post-operative serum when compared to pre-operative serum (P=0.015 and 0.029, respectively).