Identifying High-Risk Stage II Colon Cancer Patients: A Three-MicroRNA-Based Score as a Prognostic Biomarker

2016 ◽  
Vol 15 (4) ◽  
pp. e175-e182 ◽  
Author(s):  
Oriol Caritg ◽  
Alfons Navarro ◽  
Isabel Moreno ◽  
Francisco Martínez-Rodenas ◽  
Anna Cordeiro ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Prognostic Biomarker ◽  
Stage Ii ◽  
Stage Ii Colon Cancer

Abstract CT263: Post-surgical liquid biopsy-guided treatment of stage III and high-risk stage II colon cancer patients: The PEGASUS trial

2020 ◽  
Author(s):  
Elena Elez ◽  
Filippo Pietrantonio ◽  
Andrea Sartore-Bianchi ◽  
Clara Montagut ◽  
Andres Cervantes ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Ii Colon Cancer

Specific activity of cyclin dependent kinase 1 as a novel predictor of recurrence risk in stage II colon cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 402-402
Author(s):  
M. Maak ◽  
E. Zeestraten ◽  
M. Shibayama ◽  
T. Schuster ◽  
H. Friess ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Specific Activity ◽  
Risk Group ◽  
Tumor Resection ◽  
Recurrence Risk ◽  
High Risk Group ◽  
Stage Ii ◽  
Stage Ii Colon Cancer

402 Background: Altered cell cycle dynamics and check points are typical features of solid tumors, and cyclin dependent kinases (CDKs) play pivotal roles in these processes. Previously we have demonstrated that CDK-based analysis, composed of CDK1 and CDK2, is useful in the prediction of outcomes in early breast cancer patients (Ann Oncol. 19(1):68-72, 2008, Br J Cancer. 100(3):494-500, 2009). Clinically, there is a need for risk stratification in patients with stage II colon cancer who have a recurrence risk of 20 to 30%. Therefore we investigated the use of CDK-based analysis for recurrence prediction of stage II colon cancer patients. Methods: Fresh frozen tissue samples of 254 patients with histologically confirmed adenocarcinoma of the colon, UICC stage II, who received primary tumor resection in Munich (217 cases), and Leiden (37 cases) were used. Protein expression and activity of CDK1 and CDK2 were determined by in vitro assays as previously described. Specific activity (SA) of CDKs was calculated as kinase activity in relation to its corresponding mass concentration. Results: Development of distant metastasis was observed in 27 patients (10.6%) after a median follow up of 86 months. We found that predictive performance of CDK1SA, but not CDK2SA, for the metastasis was substantial and almost constant for long-term event prediction (average area under the curve (AUC) = 0.69). Tumor recurrence risk analysis in association with CDK1SA identified a low- (41% of population) and high- risk group (59%). Cox proportional hazard model analysis retained the CDK-based patient classification as an independent prognostic factor for distant metastases-free survival (low vs. high-risk group: Hazard ratio = 6.2, 95% CI: 1.45 to 26.9, p=0.0049). Clinical parameters such as grading, T-categories, age, and sex were excluded as confounding factors for CDK1SA-risk. Conclusions: CDK1SA allows stratification of different risk subgroups of stage II colon cancer patients. CDK1SA-based analysis is useful for predicting patients with high risk of distant recurrence, who should be treated with chemotherapy. No significant financial relationships to disclose.

KRAS Mutation is Associated with Worse Prognosis in Stage III or High-risk Stage II Colon Cancer Patients Treated with Adjuvant FOLFOX

2014 ◽  
Vol 22 (1) ◽  
pp. 187-194 ◽  
Author(s):  
Dae-Won Lee ◽  
Kyung Ju Kim ◽  
Sae-Won Han ◽  
Hyun Jung Lee ◽  
Ye Young Rhee ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Ii Colon Cancer ◽  
Worse Prognosis

scholarly journals Deletion of Chromosome 4q Predicts Outcome in Stage II Colon Cancer Patients

2010 ◽  
Vol 33 (2) ◽  
pp. 95-104 ◽  
Author(s):  
R. P. M. Brosens ◽  
E. J. T. H. Belt ◽  
J. C. Haan ◽  
T. E. Buffart ◽  
B. Carvalho ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Copy Number ◽  
Multiple Testing ◽  
Stage Ii ◽  
Comparative Genomic ◽  
Multiple Testing Correction ◽  
Dna Copy Number ◽  
Stage Ii Colon Cancer

Background: Around 30% of all stage II colon cancer patients will relapse and die of their disease. At present no objective parameters to identify high-risk stage II colon cancer patients, who will benefit from adjuvant chemotherapy, have been established. With traditional histopathological features definition of high-risk stage II colon cancer patients is inaccurate. Therefore more objective and robust markers for prediction of relapse are needed. DNA copy number aberrations have proven to be robust prognostic markers, but have not yet been investigated for this specific group of patients. The aim of the present study was to identify chromosomal aberrations that can predict relapse of tumor in patients with stage II colon cancer.Materials and Methods: DNA was isolated from 40 formaldehyde fixed paraffin embedded stage II colon cancer samples with extensive clinicopathological data. Samples were hybridized using Comparative Genomic Hybridization (CGH) arrays to determine DNA copy number changes and microsatellite stability was determined by PCR. To analyze differences between stage II colon cancer patients with and without relapse of tumor a Wilcoxon rank-sum test was implemented with multiple testing correction.Results: Stage II colon cancers of patients who had relapse of disease showed significantly more losses on chromosomes 4, 5, 15q, 17q and 18q. In the microsatellite stable (MSS) subgroup (n=28), only loss of chromosome 4q22.1–4q35.2 was significantly associated with disease relapse (p < 0.05, FDR < 0.15). No differences in clinicopathological characteristics between patients with and without relapse were observed.Conclusion: In the present series of MSS stage II colon cancer patients losses on 4q22.1–4q35.2 were associated with worse outcome and these genomic alterations may aid in selecting patients for adjuvant therapy.

Use of germ-line variants in the WNT/β-CATENIN pathway to predict tumor recurrence in adjuvant colon cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14034-e14034
Author(s):  
Peter M.D. Wilson ◽  
David Páez ◽  
Armin Gerger ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Tumor Recurrence ◽  
Cox Regression ◽  
Germ Line ◽  
Stage Ii ◽  
Cox Regression Analysis ◽  
Direct Dna Sequencing ◽  
Stage Ii Colon Cancer

e14034 Background: The Wnt/β-catenin signaling plays a central role in the development and progression of most colon cancers. Germline variants in Wnt/β-catenin pathway genes may result in altered gene function and/or activity, thereby causing inter-individual differences in relation to tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of Wnt/β-catenin pathway genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II colon cancer. Methods: A total of 234 patients treated with 5-fluorouracil-based chemotherapy at the University of Southern California were included in this study. Whole blood samples were analyzed for putative functional germline polymorphisms in SFRP3, SFRP4, DKK2, DKK3, Axin2, APC, TCF7L2, WNT5B, CXXC4 genes by PCR-RFLP or direct DNA-sequencing. We also included NOTCH2 and GLI1 variants which belong to the Notch and Hedgehog pathways respectively. Results: The minor allele of WNT5B rs2010851 T>G was significantly associated with a shorter TTR (4.9vs10.7 years; HR: 2.48; 95%CI, (0.96, 6.38); p=0.044) in high-risk stage II colon cancer patients. This result remained significant in the multivariate Cox regression analysis. Conclusions: Despite the importance of Wnt/β-catenin pathway in the development of cancer, only the WNT5B germline variant rs2010851 was significantly identified as a stage-dependent prognostic marker for colon cancer patients after 5-fluorouracil-based adjuvant therapy.

scholarly journals Prognostic value of nucleotyping, DNA ploidy and stroma in high-risk stage II colon cancer

2020 ◽  
Vol 123 (6) ◽  
pp. 973-981 ◽  
Author(s):  
Lujing Yang ◽  
Pengju Chen ◽  
Li Zhang ◽  
Lin Wang ◽  
Tingting Sun ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Dna Ploidy ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Contributory Factor ◽  
Stage Ii Colon Cancer

Abstract Background Heterogeneity with respect to recurrence and survival in high-risk stage II colon cancer patients still exists, and further classification is urgently required. This study aimed to ascertain the prognostic value of DNA ploidy, stroma-tumour fraction and nucleotyping in the prognosis of high-risk stage II colon cancer. Methods A total of 188 high-risk stage II colon cancer patients received radical surgery in Peking University Cancer Hospital, from 2009 to 2015. Status of mismatch repair proteins in tumours was analysed using immunohistochemistry. DNA ploidy, stroma-tumour fraction and nucleotyping were estimated by automated digital imaging systems. Results Nucleotyping and DNA ploidy were significant prognostic factors, while stroma-tumour fraction were not significantly prognostic in the univariate analysis. In the multivariable model, the dominant contributory factor of disease-free survival was chromatin heterogeneous vs. chromatin homogeneous [HR 3.309 (95% CI: 1.668–6.564), P = 0.001]. Conclusions Our study indicates that nucleotyping is an independent prognostic factor in high-risk stage II colon cancer. Therefore, it may help subdivide patients into different subgroups and give them different strategies for follow-up and treatment in the future.

scholarly journals Identification of Risk Factors for Recurrence in High-Risk Stage II Colon Cancer

10.9738/cc131 ◽  
2013 ◽  
Vol 98 (2) ◽  
pp. 114-121 ◽  
Author(s):  
Satoshi Hatano ◽  
Hideyuki Ishida ◽  
Keiichiro Ishibashi ◽  
Kensuke Kumamoto ◽  
Norihiro Haga ◽  
...  
Keyword(s):  
Risk Factors ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Cox Proportional Hazards ◽  
Stage Ii ◽  
Risk Factors For Recurrence ◽  
Stage Ii Colon Cancer

Abstract To identify risk factors for recurrence in patients with stage II colon cancer, Cox proportional hazards regression analysis was performed in 194 patients with stage II colon cancer who underwent curative surgery between April 1997 and December 2008. Thirteen clinical and pathologic factors, including use of fluoropyrimidine-based adjuvant chemotherapy in 113 of the patients (58.2%), were assessed. By multivariate analysis, only obstruction, perforation, and T4-level invasion were identified as independent risk factors affecting disease-free survival (DFS) (P &lt; 0.01). The 5-year DFS rate was 70.6% in patients with one or more risk factors (n = 68) and 96.0% in patients with no risk factors (n = 126) (P &lt; 0.01). These results suggest that obstruction, perforation, and T4-level invasion are suitable candidates for prediction of tumor recurrence in patients with stage II colon cancer. The oxaliplatin-based adjuvant chemotherapy, which has been reported to be effective in stage III colon cancer patients, may improve the prognosis in high-risk stage II colon cancer patients.

The prognostic importance of miRNA-21 in stage II colon cancer: A population-based study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3513-3513
Author(s):  
Sanne Kjaer-Frifeldt ◽  
Torben Hansen ◽  
Boye Schnack Nielsen ◽  
Stine Joergensen ◽  
Jan Lindebjerg ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Population Based ◽  
Stage Ii ◽  
Stromal Compartment ◽  
Cox Regression Analysis ◽  
Prognostic Importance ◽  
Stage Ii Colon Cancer

3513 Background: Adjuvant chemotherapy for stage II colon cancer patients is still controversial and the debate on which patients should be considered as high risk patients is still ongoing. The decision is based on clinical and pathological markers of risk, which are inadequately informative in most of the patients, and better methods are highly needed. The aim of the present study was to investigate the possible prognostic importance of miRNA-21, quantified by in situ hybridization (ISH), in a unique, large population-based cohort of patients treated for stage II colon cancer patients. Methods: The study included all patients diagnosed with stage II colon cancer in Denmark in the year 2003 (711 patients), representing a full population of five million people. Patients receiving adjuvant chemotherapy were excluded (N=15). One paraffin-embedded tissue block was obtained from each patient. A 6μm-thick section was processed for formazan-based chromogenic miR-21 ISH analysis and counter stained with nuclear red. The blue miR-21 ISH signal was assessed by image analysis to obtain two quantitative expression estimates: the total blue area (TB) and the ratio of TB with the nuclear density (TBR). Results: The miRNA-21 signal was predominantly observed in fibroblast-like cells located in the stromal compartment of the tumors. Patients expressing high levels of miRNA-21 (high mean TBR) had significantly inferior cancer specific survival (CSS): HR = 1.26 (95% CI; 1.15-1.60), p <0.001. In the COX regression analysis (including; gender, T-category, malignancy grade, localization, tumor perforation, tumor fixation, number of lymph nodes and MSI status), mean TBR was found to be an independent predictive marker of poor CSS, HR = 1.41 (95%CI; 1.19-1.67, p< 0.001). The same applied to TB. Conclusions: The present study shows that increasing miRNA-21 expression level is significantly correlated to decreasing CSS. Analyses of miRNA-21 should be considered as a potential adjunct in the selection of high risk stage II patients.

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