Prognosis of lung metastases of colorectal cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Lung Metastases Of Colorectal Cancer
PROVIDER: 2740883 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
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: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: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: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:In this study, we aimed to assess the prognostic value of CD226 on tumor-infiltrating lymphocytes derived from liver metastases of colorectal cancer (CRC) patients treated with chemotherapy and radical surgery. CD226high expression was associated with a potent immune infiltrate in RNAseq from primary colorectal cancer and liver metastases. CD226 expression contributes to defining the immune contexture of CRC liver metastases and primary tumors. In liver metastases, CD226 expression on CD8 T cells was not specifically co-expressed with other immune checkpoints such as PD1, TIGIT and TIM3. Multivariate Cox regression analysis revealed that CD226 expression on CD8 T cells was an independent prognostic factor (p=0.003) along with CD3 density at invasion margins (p=0.003) and TIGIT expression on CD4 T cells (p=0.019). CD155 was not associated with CD226 prognostic value. Gene expression analysis in a validation dataset confirmed the prognostic value of CD226 selectively in liver metastases but not in primary tumors. Down regulation of CD226 on CD8+ infiltrating lymphocytes in liver microenvironment might be restored by IL-15 treatment. CD226 expression on liver metastases-infiltrating CD8+ contributes selectively to the immune surveillance of liver metastases from CRC and displays a prognostic value for patients undergoing radical surgery.
2022-12-01 | GSE207194 | GEO
Project description:Initial screening for potential metastases suppressors down regulated by methylation was performed using lung cancer cell line models specific for site-specific metastasation. Gene expression profiling and qRT-PCR validations were conducted on tumor tissues from primary lung cancer (LC) and brain metastasis. HERC5 was further characterized for the methylation pattern.
2014-11-18 | GSE57492 | GEO
Project description:We obtained primary lesions, brain metastases, and normal lung tissues from lung adenocarcinoma patients. Next generation sequencing was performed to assess the expressions of miRNA in these specimens.
2023-04-26 | GSE230229 | GEO
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.
2014-02-10 | GSE38479 | GEO
Project description:By transcriptionally profiling single cells from patients spanning different stages of lung adenocarcinoma progression, we provide evidence of epithelial regeneration in untreated primary tumours and a continuum of phenotypic states spanning key stages of embryonic development and lung morphogenesis in metastases. We transcriptionally profiled 41,384 single cells obtained from fresh surgical human samples taken from non-tumour-involved lung (n = 4), primary lung adenocarcinomas (n = 8; 7 untreated and 1 post neo-adjuvant chemotherapy), as well as brain (n = 3), bone (n = 1), and adrenal (n = 1) lung adenocarcinoma metastases. These samples were derived from patients spanning various stages of tumour progression without enrichment for a specific cell type, such that the entire tumour and its microenvironment were sampled in an unbiased manner. Data from all patients were merged to create a global cell atlas of the normal lung, primary tumours, and metastases.
2020-01-14 | GSE123902 | 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