Project description:We obtained fibroblast cultures from fresh surgical specimen ressected from patients with primary colorectal carcinoma: normal colonic fibroblasts (NCF=9) from the normal colonic mucosa at least 5-10cm from the surgical margin, carcinoma-associated fibroblasts from the primary tumor (CAF-PT=14) and carcinoma-associated fibroblasts (CAF-LM=11) from fresh surgical specimens of liver metastases. We identified 277 probes, in common between the three types of fibroblasts, whose expression level is sequentially deregulated according to cancer progression (NCF→CAF-PT→CAF-LM; fold change Log2 normalized expression>1.5 in each step). Prediction Analysis of Microarrays was applied to obtain a 25-gene signature that better characterizes each fibroblast class. The signature is able to classify patients carrying primary tumors according to prognosis. This fact was exploited to obtain a 19-gene signature (from the 277 deregulated probes) predicting recurrence with high accuracy in stage II/III colorectal cancer patients. Signature validation has been carried out in two independent datasets and in a meta-cohort of 336 stage II/III patients. Since the 25-gene signature was obtained regardless of gene expression data of tumor specimens or patient’s clinical data, the prognostic power of this signature provides strong evidence of the link between the tumor stroma and cancer progression. Furthermore, the 19-gene signature was able to identify low-risk patients with very high accuracy, especially relevant for those high-risk stage-II patients. We hybridised fibroblast RNA in Affymetrix GeneChip 1.0 st arrays
Project description:We obtained fibroblast cultures from fresh surgical specimen ressected from patients with primary colorectal carcinoma: normal colonic fibroblasts (NCF=9) from the normal colonic mucosa at least 5-10cm from the surgical margin, carcinoma-associated fibroblasts from the primary tumor (CAF-PT=14) and carcinoma-associated fibroblasts (CAF-LM=11) from fresh surgical specimens of liver metastases. We identified 277 probes, in common between the three types of fibroblasts, whose expression level is sequentially deregulated according to cancer progression (NCF→CAF-PT→CAF-LM; fold change Log2 normalized expression>1.5 in each step). Prediction Analysis of Microarrays was applied to obtain a 25-gene signature that better characterizes each fibroblast class. The signature is able to classify patients carrying primary tumors according to prognosis. This fact was exploited to obtain a 19-gene signature (from the 277 deregulated probes) predicting recurrence with high accuracy in stage II/III colorectal cancer patients. Signature validation has been carried out in two independent datasets and in a meta-cohort of 336 stage II/III patients. Since the 25-gene signature was obtained regardless of gene expression data of tumor specimens or patient’s clinical data, the prognostic power of this signature provides strong evidence of the link between the tumor stroma and cancer progression. Furthermore, the 19-gene signature was able to identify low-risk patients with very high accuracy, especially relevant for those high-risk stage-II patients.
2013-05-10 | GSE46824 | GEO
Project description:Molecular subtyping of stage II/III colorectal cancer with poor outcome
Project description:High-throughput proteomics profiling-derived signature associated with chemotherapy response and survival for stage II/III colorectal cancer
Project description:Defining molecular features that can predict the response to chemotherapy for stage II-III colorectal cancer (CRC) patients remains challenging in cancer research. Most available clinical samples are Formalin-Fixed and Paraffin-Embedded (FFPE). Affymetrix GeneChip® Human Transcriptome Array 2.0 (HTA) is one platform marketed for high-throughput gene expression profiling for FFPE tissue samples. In this study, we analyzed the whole transcriptom gene expression of 156 CRC patient samples measured by this platform to identify biomarkers predicting the response to chemotherapy for stage II-III CRC patients.
Project description:To search for potential miRNAs associated with prognosis in colorectal carcinoma, miRNA expression profiles were analyzed in patients with stage III colorectal carcinoma. miRNA expression levels were compared between long and short time survival after surgery with standard chemotherapy.
Project description:Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second leading cause of cancer death globally. The molecular mechanisms underlying CRC have been investigated using different omics technologies including genomics, proteomics, and metabolomics. Resulting molecular signatures can be employed to stratify CRC patients and aid decisions about therapies or evaluate prognostic outcome. However, molecular biomarkers for identification of patients at increased risk of disease recurrence are currently lacking. Here, we present a comprehensive multi-omics analysis of a Danish colorectal cancer tumor cohort composed of 412 biopsies from tumors of 371 patients diagnosed at stage II or III. We identified microsatellite instability and tumor stage as the two main clinical traits statistically linked to the risk of relapse. Integrating proteomics and transcriptomics data, we classified the tumors into four consensus molecular subtypes, and found that stage III tumors showed higher epithelial-to-mesenchymal transition signature than stage II. As the mesenchymal-like subtype is the one with most invasive and metastatic phenotype, we focused on proteins over-expressed in this subtype and evaluated their potential as relapse-free survival markers. Specifically, we studied on the role of CAVIN1 in the formation and progression of colorectal cancer in a 3D in vitro model. Finally, using hybrid-DIA phosphoproteomics profiling we identified an mTOR kinase activity footprint that was specific to patients that suffered post-surgery relapse. Compared to previous omics analysis of CRC, our multi-omics classification provided deeper insights into the mesenchymal-like subtypes with stronger correlations with risk of relapse.
Project description:Purpose: A 128-gene signature has been proposed to predict poor outcomes in patients with stage II and III colorectal cancer. In the present study we aimed to validate this previously published 128-gene signature on external and independent data from patients with stage II and III colon cancer.