Ceramides Profile Identifies Patients with More Advanced Stages of Colorectal Cancer

Much attention is paid to different sphingolipid pathways because of their possible use in diagnostics and treatment. However, the activity status and significance of ceramide pathways in colorectal cancer are still unclear. We analyzed colorectal cancer patients to evaluate sphingolipid profiles in the blood, colorectal cancer (CRC) tissues, and healthy surrounding colorectal tissues of the same patient, simultaneously, using liquid chromatography coupled with triple quadrupole mass spectrometry. Furthermore, we measured protein expression of de novo ceramide synthesis enzymes and mitochondrial markers in tissues using western blot. We confirmed the different sphingolipid contents in colorectal cancer tissue compared to healthy surrounding tissues. Furthermore, we showed changed amounts of several ceramides in more advanced colorectal cancer tissue and found a prominently higher circulating level of several of them. Moreover, we observed a relationship between the amounts of some ceramide species in colorectal cancer tissue and plasma depending on the stage of colorectal cancer according to TNM (tumors, nodes, metastasis) classification. We think that the combined measurement of several ceramide concentrations in plasma can help distinguish early-stage lesions from advanced colorectal cancer and can help produce a screening test to detect early colorectal cancer.

Download Full-text

Gene Expression Signature in Advanced Colorectal Cancer Patients Select Drugs and Response for the Use of Leucovorin, Fluorouracil, and Irinotecan

Journal of Clinical Oncology ◽

10.1200/jco.2006.07.4187 ◽

2007 ◽

Vol 25 (7) ◽

pp. 773-780 ◽

Cited By ~ 118

Author(s):

Maguy Del Rio ◽

Franck Molina ◽

Caroline Bascoul-Mollevi ◽

Virginie Copois ◽

Frédéric Bibeau ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Cancer Patients ◽

Advanced Colorectal Cancer ◽

Support Vector ◽

Cancer Tissue ◽

Chemotherapy Response ◽

First Line ◽

Metastatic Setting ◽

Colorectal Cancer Patients

Purpose In 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.

Download Full-text

Urine Metabolite Profiling of Human Colorectal Cancer by Capillary Electrophoresis Mass Spectrometry Based on MRB

Gastroenterology Research and Practice ◽

10.1155/2012/125890 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 14

Author(s):

Jin-Lian Chen ◽

Jing Fan ◽

Liu-Shui Yan ◽

Hui-Qin Guo ◽

Jing-Jing Xiong ◽

...

Keyword(s):

Colorectal Cancer ◽

Mass Spectrometry ◽

Capillary Electrophoresis ◽

Cancer Patients ◽

Advanced Colorectal Cancer ◽

Early Stage ◽

Urine Samples ◽

Urine Metabolites ◽

Colorectal Cancer Patients ◽

Capillary Electrophoresis Mass Spectrometry

Aim. The study was to investigate the metabolic profile of urine metabolites and to elucidate their clinical significance in patients with colorectal cancer.Methods. Colorectal cancers from early stage and advanced stage were used in this study. Urine samples of colorectal cancer patients and healthy adults were collected and subjected to capillary electrophoresis mass spectrometry based on moving reaction boundary analysis. The metabolic data were analyzed by SPSS 17.0 to find urinary biomarkers for colorectal cancer.Results. The results indicated that the urine metabolic profiling of colorectal cancer patients had significant changes compared with the normal controls, and there were also differences between early stage and advanced colorectal cancer patients. Compared with the control group, the levels of isoleucine, valine, arginine, lactate acid and leucine increased(P<0.05), but those of histidine, methionine, serine, aspartic acid, citric acid, succinate, and malic acid decreased in urine samples from colorectal cancer(P<0.05). Furthermore, the levels of isoleucine and valine were lower in urine of patients with advanced colorectal cancer than those in early stage colorectal cancer(P<0.05).Conclusion. The technique of capillary electrophoresis mass spectrometry based on MRB could reveal the significant metabolic alterations during progression of colorectal cancer, and the method is feasible and may be useful for the early diagnosis of colorectal cancer.

Download Full-text