Identification of subtypes in colorectal cancer and their prognostic values

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4041-4041
Author(s):  
R. D. Kennedy ◽  
V. Proutski ◽  
A. Tanney ◽  
A. Winter ◽  
J. M. Black ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Subtypes ◽  
Cpg Island ◽  
Microarray Platform ◽  
Molecular Classification ◽  
Disease Classification ◽  
Stage Ii ◽  
Cpg Island Methylator Phenotype ◽  
Cancer Disease ◽  
Stage Ii Colorectal Cancer

4041 Background: The discovery and widespread acceptance of molecular subtypes in breast cancer has changed the way that this disease is viewed. Similarly, we have focussed on stage II colorectal cancer where 20–25% of patients are at risk of recurrent disease following surgery. There are currently several types of colorectal cancer recognised by histopathological methods, however, little has been published regarding disease classification at a molecular level. Methods: We have taken an unbiased approach to the molecular classification of colorectal cancer. Using a colorectal cancer disease specific microarray platform we have performed expression profiling and bioinformatic analysis of 500 formalin fixed and paraffin embedded (FFPE) stage II colorectal cancer samples, in order to identify and characterise molecular subtypes. Results: We have identified molecular subtypes for colorectal cancer. One of these subtypes is enriched with tumours with microsatellite instability (MSI) that are predominantly proximal, mucinous and poorly differentiated. It is notable that while MSI is generally accepted to be associated with a good prognosis, we have found both good and poor prognosis patients within this subtype. A second subtype contains tumors with a low CpG island methylator phenotype. Another subtype is defined by an expression pattern consistent with activation of tumor suppressors. The remaining subtypes are newly identified. Conclusions: We have identified molecular subtypes in colorectal cancer. We will present how knowledge about these subtypes may affect patient management and may be used to guide the development of novel therapeutic strategies. [Table: see text]

scholarly journals MAPT promoter CpG island hypermethylation is associated with poor prognosis in patients with stage II colorectal cancer

2019 ◽  
Vol Volume 11 ◽  
pp. 7337-7343 ◽  
Author(s):  
Chuntao Wang ◽  
Yanliang Liu ◽  
Wenyi Guo ◽  
Xu Zhu ◽  
Nita Ahuja ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Cpg Island ◽  
Stage Ii ◽  
Stage Ii Colorectal Cancer

scholarly journals Molecular Subtypes of Colorectal Cancer and Their Clinicopathologic Features, With an Emphasis on the Serrated Neoplasia Pathway

2016 ◽  
Vol 140 (5) ◽  
pp. 406-412 ◽  
Author(s):  
Jeong Mo Bae ◽  
Jung Ho Kim ◽  
Gyeong Hoon Kang
Keyword(s):  
Colorectal Cancer ◽  
Complex Disease ◽  
Molecular Subtypes ◽  
Cpg Island ◽  
Colorectal Cancers ◽  
Cpg Island Methylator Phenotype ◽  
Molecular Features ◽  
Methylator Phenotype ◽  
Serrated Neoplasia Pathway ◽  
Molecular Carcinogenesis

Context.—Colorectal cancer is a heterogeneous disease entity with 3 molecular carcinogenesis pathways and 2 morphologic multistep pathways. Right-sided colon cancers and left-sided colon and rectal cancers exhibit differences in their incidence rates according to geographic region, age, and sex. A linear tendency toward increasing frequencies of microsatellite instability–high or CpG island methylator phenotype–high cancers in subsites along the bowel from the rectum to the cecum or the ascending colon accounts for the differences in tumor phenotypes associated with these subsites. The molecular subtypes of colorectal cancers exhibit different responses to adjuvant therapy, which might be responsible for differences in subtype-specific survival. Objectives.—To review the clinicopathologic and molecular features of the molecular subtypes of colorectal cancer generated by combined CpG island methylator phenotype and microsatellite statuses, to integrate these features with the most recent findings in the context of the prognostic implications of molecular subtypes, and to emphasize the necessity of developing molecular markers that enable the identification of adenocarcinomas involving the serrated neoplasia pathway. Data Sources.—Based on the authors' own experimental data and a review of the pertinent literature. Conclusions.—Because colorectal cancers arise from 2 different morphologic multistep carcinogenesis pathways with varying contributions from 3 different molecular carcinogenesis pathways, colorectal cancer is a heterogeneous and complex disease. Thus, molecular subtyping of colorectal cancers is an important approach to characterizing their heterogeneity with respect to not only prognosis and therapeutic response but also biology and natural history.

scholarly journals Promoter CpG island methylation of RET predicts poor prognosis in stage II colorectal cancer patients

2014 ◽  
Vol 8 (3) ◽  
pp. 679-688 ◽  
Author(s):  
Muriel X.G. Draht ◽  
Kim M. Smits ◽  
Benjamin Tournier ◽  
Valerie Jooste ◽  
Caroline Chapusot ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Cpg Island ◽  
Stage Ii ◽  
Stage Ii Colorectal Cancer ◽  
Cpg Island Methylation ◽  
Colorectal Cancer Patients

A genetic signature of relapse in stage II colorectal cancer derived from formalin fixed paraffin embedded tissue (FFPE) tissue using a unique disease specific colorectal array

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3519-3519 ◽  
Author(s):  
P. G. Johnston ◽  
K. Mulligan ◽  
E. Kay ◽  
J. Black ◽  
S. Moore ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Signature ◽  
Ffpe Tissue ◽  
Stage Ii ◽  
Cancer Disease ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Ffpe Tissues ◽  
Stage Ii Colorectal Cancer ◽  
Disease Specific

3519 Background: We have developed the first disease specific microarray for colorectal cancer using a transcriptome-based approach. This unique tool has been specially designed and optimised for analysis of gene expression profiles from formalin fixed paraffin embedded tissues (FFPE). To evaluate this tool we are conducting a study in patients with Dukes B (stage II) colorectal cancer (CRC) using FFPE tissues to determine a prognostic genetic signature predicting disease recurrence. Methods: The colorectal array was developed using a high-throughput transcriptome-based approach and encodes over 52,500 transcripts expressed in normal and diseased colorectal tissue. To date, tumours from 32 patients have been selected (mean FFPE tissue block age - 10.4 years) from the stage II CRC cohort of a phase III randomized trial comparing 5-FU/Leucovorin versus no adjuvant treatment (NI240). The patients were from the observation alone arm;19 of whom were disease-free for 5 years post-randomisation, while 13 suffered relapse prior to 3 years. Results: RNA was extracted from all 32 FFPE tissue samples, amplified, labelled and hybridised to the colorectal cancer disease specific array. Raw data was normalised using scalar, median-polish and z-score strategies and scalar was selected as the best strategy in relation to predictive error. Within this data set genes selected by correlation using ANOVA performed best in both KNN and support vector machine algorithms (supervised). Using this approach a gene signature containing 48 genes demonstrated 100% accuracy in the prediction of relapse in stage II CRC (p<0.001). This signature was also able to separate samples at the meta-node level using unsupervised hierarchical clustering. Conclusion: We have developed the first colorectal cancer disease specific microarray and demonstrated its use using FFPE tissues. Using this approach we have derived a gene signature that predicts for a high likelihood of early relapse in stage II CRC. [Table: see text]

scholarly journals Prognostic and Predictive Value of CpG Island Methylator Phenotype in Patients with Locally Advanced Nonmetastatic Sporadic Colorectal Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Yuwei Wang ◽  
Yadong Long ◽  
Ye Xu ◽  
Zuqing Guan ◽  
Peng Lian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Cpg Island ◽  
Locally Advanced ◽  
Stage Ii ◽  
Sporadic Colorectal Cancer ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype ◽  
Colorectal Cancer Patients

Purpose. In the present study, the prognostic significance of CpG island methylator phenotype (CIMP) in stage II/III sporadic colorectal cancer was evaluated using a five-gene panel.Methods. Fifty stage II/III colorectal cancer patients who received radical resection were included in this study. Promoter methylation of p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 was determined by methylation specific polymerase chain reaction (MSP). CIMP positive was defined as hypermethylation of three or more of the five genes. Impact factors on disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier method (log-rank test) and adjusted Cox proportional hazards model.Results. Twenty-four percent (12/50) of patients were characterized as CIMP positive. Univariate analysis showed stage III (P=0.049) and CIMP positive (P=0.014) patients who had significantly inferior DFS. In Cox regression analysis, CIMP positive epigenotype was independently related with poor DFS with HR = 2.935 and 95% CI: 1.193–7.220 (P=0.019). In patients with CIMP positive tumor, those receiving adjuvant chemotherapy had a poor DFS than those without adjuvant chemotherapy (P=0.023).Conclusions. CIMP positive was significantly correlated with decreased DFS in stage II/III colorectal cancer. Patients with CIMP positive locally advanced sporadic colorectal cancers may not benefit from 5-fluorouracil based adjuvant chemotherapy.

Sign in / Sign up

Export Citation Format

Share Document