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.
Specific extracellular matrix remodeling signature of colon hepatic metastases.
Sex, Age, Specimen part, Subject
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Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.
Sex, Age
View SamplesWe report that previously described molecular subtypes of colorectal cancer are associated with the response to therapy in patients with metastatic disease. We also identified a patient population with high FOLFIRI sensitivity, as indicated by their 2.7-fold longer overall survival when treated with FOLFIRI, as first-line regimen, instead of FOLFOX. Our results demonstrate the interest of molecular classifications to develop tailored therapies for patients with metastatic colorectal cancer.
Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.
Sex, Age
View SamplesWe report that previously described molecular subtypes of colorectal cancer are associated with the response to therapy in patients with metastatic disease. We also identified a patient population with high FOLFIRI sensitivity, as indicated by their 2.7-fold longer overall survival when treated with FOLFIRI, as first-line regimen, instead of FOLFOX. Our results demonstrate the interest of molecular classifications to develop tailored therapies for patients with metastatic colorectal cancer.
Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
Sex, Age, Specimen part, Subject
View SamplesTo 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.
Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
Sex, Age, Specimen part, Subject
View SamplesIn patients with advanced colorectal cancer, leucovorin, fluorouracil, and irinotecan (FOLFIRI) is considered as one of the reference first-line treatments. However, only about half of treated patients respond to this regimen, and there is no clinically useful marker that predicts response. A major clinical challenge is to identify the subset of patients who could benefit from this chemotherapy. We aimed to identify a gene expression profile in primary colon cancer tissue that could predict chemotherapy response. Patients and Methods:- Tumor colon samples from 21 patients with advanced colorectal cancer were analyzed for gene expression profiling using Human Genome GeneChip arrays U133. At the end of the first-line treatment, the best observed response, according to WHO criteria, was used to define the responders and nonresponders. Discriminatory genes were first selected by the significance analysis of microarrays algorithm and the area under the receiver operating characteristic curve. A predictor classifier was then constructed using support vector machines. Finally, leave-one-out cross validation was used to estimate the performance and the accuracy of the output class prediction rule. Results:- We determined a set of 14 predictor genes of response to FOLFIRI. Nine of nine responders (100% specificity) and 11 of 12 nonresponders (92% sensitivity) were classified correctly, for an overall accuracy of 95%. Conclusion:- After validation in an independent cohort of patients, our gene signature could be used as a decision tool to assist oncologists in selecting colorectal cancer patients who could benefit from FOLFIRI chemotherapy, both in the adjuvant and the first-line metastatic setting.
Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
Specimen part
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