DNA copy number alterations, gene expression changes and disease-free survival in patients with colorectal cancer: a 10 year follow-up

2016 ◽  
Vol 39 (6) ◽  
pp. 545-558 ◽  
Author(s):  
Elisabetta Bigagli ◽  
Carlotta De Filippo ◽  
Cinzia Castagnini ◽  
Simona Toti ◽  
Francesco Acquadro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Copy Number ◽  
Disease Free Survival ◽  
Copy Number Alterations ◽  
Dna Copy Number ◽  
Free Survival ◽  
Dna Copy Number Alterations ◽  
Disease Free

scholarly journals TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Sha Zhou ◽  
Jianhong Peng ◽  
Liuniu Xiao ◽  
Caixia Zhou ◽  
Yujing Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Free Survival ◽  
Epigenetic Regulator ◽  
Crc Management ◽  
Disease Free ◽  
Resistance To Chemotherapy

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

Radiofrequency Ablation of Hepatic Metastases from Colorectal Cancer: Are Newer Generation Probes Better?

2006 ◽  
Vol 72 (10) ◽  
pp. 875-879 ◽  
Author(s):  
Aziz Ahmad ◽  
Steven L. Chen ◽  
Maihgan A. Kavanagh ◽  
David P. Allegra ◽  
Anton J. Bilchik
Keyword(s):  
Colorectal Cancer ◽  
Radiofrequency Ablation ◽  
First Generation ◽  
Hepatic Metastases ◽  
Disease Free Survival ◽  
Cancer Center ◽  
Free Survival ◽  
Alive With Disease ◽  
Disease Free

Second-generation radiofrequency ablation (RFA) probes and their successors have more power, shorter ablation times, and an increased area of ablation compared with the first-generation probes used before 2000. We examined whether the use of the newer probes has improved the clinical outcome of RFA for hepatic metastases of colorectal cancer at our tertiary cancer center. Of 160 patients who underwent RFA between 1997 and 2003, 52 had metastases confined to the liver: 21 patients underwent 46 ablations with the first-generation probes and 31 patients underwent 58 ablations with the newer probes. The two groups had similar demographic characteristics. At a median follow-up of 26.2 months, patients treated with the newer probes had a longer median disease-free survival (16 months vs 8 months, P < 0.01) and a lower rate of margin recurrence (5.2% vs 17.4%); eight patients had no evidence of disease and one patient was alive with disease. By contrast, of the 46 patients treated with the first-generation probes, 2 patients had no evidence of disease and 1 patient was alive with disease. Newer-generation probes are associated with lower rates of margin recurrence and higher rates of disease-free survival after RFA of hepatic metastases from colorectal cancer.

scholarly journals Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer

2019 ◽  
Vol 47 (5) ◽  
pp. 1829-1842 ◽  
Author(s):  
Weimin Xu ◽  
Yilian Zhu ◽  
Wei Shen ◽  
Wenjun Ding ◽  
Tingyu Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
T Stage ◽  
Cdx2 Expression ◽  
Prognostic Prediction ◽  
Disease Free

Objective Prognostic prediction of colorectal cancer (CRC) remains challenging because of its heterogeneity. Aberrant expression of caudal-type homeobox transcription factor 2 (CDX2) is strongly correlated with the prognosis of CRC. Methods Tissue samples of patients with CRC who underwent surgery in Xinhua Hospital (Shanghai, China) from January 2010 to January 2013 were collected. CDX2 expression was semiquantitatively evaluated via immunohistochemistry. Results In total, 138 patients were enrolled in this study from a prospectively maintained institutional cancer database. The median follow-up duration was 57.5 months (interquartile range, 17.0–71.0 months). In the Cox proportional hazards model, low CDX2 expression combined with stage T4 CRC was significantly the worst prognostic factor for disease-free survival (hazard ratio = 7.020, 95% confidence interval = 3.922–12.564) and overall survival (hazard ratio = 5.176, 95% CI = 3.237–10.091). In the Kaplan–Meier survival analysis, patients with low CDX2 expression and stage T4 CRC showed significantly worse disease-free survival and overall survival than those with low CDX2 expression alone. Conclusion CDX2 expression combined with the T stage was more accurate for predicting the prognosis of CRC. Determining the prognosis of CRC using more than one variable is valuable in developing appropriate treatment and follow-up strategies.

Cure rate in early colorectal cancer estimated from disease-free survival curves from phase III comparative clinical trials: Necessity of long follow-up

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15006-e15006
Author(s):  
E. Barrajon ◽  
A. Lopez ◽  
G. Esquerdo ◽  
J. M. Cervera
Keyword(s):  
Colorectal Cancer ◽  
Event Rate ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Early Colorectal Cancer ◽  
Cure Rate ◽  
Survival Curves ◽  
Free Survival ◽  
Disease Free

e15006 Background: The traditional end point for adjuvant clinical trials is overall survival (OS). Short-term disease-free survival (DFS) has been accepted as a surrogate of 5-year OS in colorectal cancer trials. Nevertheless, recent adjuvant trials have not shown a consistent improvement in OS despite a significant improvement in DFS. Two reasons may explain this effect: 1) a delay in relapse produced by treatment, not affecting the cure rate, or 2) more effective treatments in relapsing patients which delay death, hiding a real difference in cure rates. The aim of this project is to study the relationship between DFS and OS in trials of early colorectal cancer. Methods: Phase III comparative trials in colorectal cancer were searched in databases and cancer meetings. Trials were split to build and validate the model. United States 2000 population life table data were obtained from Berkeley Mortality Database. Survival curves were modelled according to a cured fraction following a Weibull distribution and a relapsing fraction following a binomial distribution. DFS was modelled as time to a single event and OS was modelled as time to two events. Cured fraction was estimated and odds ratio (OR) with 95% confidence interval was calculated for experimental arms. Time to achieve a plateau in DFS was estimated as the curve point with a risk of relapse below 1%. Regression analysis between DFS and OS was performed for different intervals of follow up. Results: Thirty six study arms reporting DFS were analyzed to build the model. The model is consistent with an annual event rate of 0.33. DFS curves with this event rate predict a mean cure rate of 0.58 (range: 0.11–0.73). Estimated time to achieve a plateau in DFS is 9.3 years (range: 8.3–11.2 years). Significance of OR is coherent with hazard ratio reported in the studies. Trials finished after 1999 show more OS related to DFS. Regression analysis between DFS and OS show changing parameters at different intervals of follow up and some non-linearities. Trial validation, and analysis with trials reporting relapse free survival will be presented. Conclusions: Follow up of up to 10 years in colon adjuvant trials appears to be appropriate to reliably detect benefit in OS instead of a delay effect on relapse. No significant financial relationships to disclose.

scholarly journals Folate pathway genes linked to mitochondrial biogenesis and respiration are associated with outcome of patients with stage III colorectal cancer

Tumor Biology ◽  
2019 ◽  
Vol 41 (6) ◽  
pp. 101042831984623 ◽  
Author(s):  
Elisabeth Odin ◽  
Arvid Sondén ◽  
Göran Carlsson ◽  
Bengt Gustavsson ◽  
Yvonne Wettergren
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Mitochondrial Biogenesis ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Free Survival ◽  
Folate Pathway ◽  
Colorectal Cancer Patients ◽  
Disease Free

5-fluorouracil in combination with the folate leucovorin is the cornerstone in treatment of colorectal cancer. Transport of leucovorin into cells, and subsequent metabolic action, require expression of several genes. The aim was to analyze if tumoral expression of genes putatively involved in leucovorin transport, polyglutamation, or metabolism was associated with outcome of patients with stage III colorectal cancer treated with adjuvant chemotherapy. A total of 363 stage III colorectal cancer patients who received adjuvant bolus 5-fluorouracil + leucovorin alone, or in combination with oxaliplatin according to Nordic bolus regimes were included. Expression of 11 folate pathway genes was determined in tumors using quantitative real-time polymerase chain reaction and related to disease-free survival. The median follow-up time was 5 years. During follow-up, 114 (31%) patients suffered from recurrent disease. A high tumoral expression of the genes SLC46A1/PCFT, SLC19A1/RFC-1, ABCC3/MRP3, GGH, and MTHFD1L, which are involved in folate transport, polyglutamation, or metabolism, was associated with longer disease-free survival of the patients. Each of these genes either encodes mitochondrial enzymes or is being regulated by mitochondrial transcription factors. Expression of the SLC46A1/PCFT gene was most strongly associated with disease-free survival, regardless of treatment regimen. In conclusion, the results show that expression of folate pathway genes are associated with outcome of colorectal cancer patients treated with adjuvant 5-fluorouracil in combination with leucovorin. A prospective study needs to be conducted to determine if expression of these genes can be used to predict response to leucovorin and other folates that are now being tested in clinical studies. Moreover, there seems to be a link between folate metabolism and mitochondrial biogenesis and respiration that deserves further exploration.

scholarly journals Exploring Gene Expression Signatures for Predicting Disease Free Survival after Resection of Colorectal Cancer Liver Metastases

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49442 ◽  
Author(s):  
Nikol Snoeren ◽  
Sander R. van Hooff ◽  
Rene Adam ◽  
Richard van Hillegersberg ◽  
Emile E. Voest ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Liver Metastases ◽  
Disease Free Survival ◽  
Colorectal Cancer Liver Metastases ◽  
Free Survival ◽  
Gene Expression Signatures ◽  
Disease Free

Generation and application of a colorectal cancer microarray library to identify a novel prognostic biomarker, adipose differentiation related protein (adipophilin).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 508-508
Author(s):  
John Hogan ◽  
Laura O Byrne ◽  
Michael O Callaghan ◽  
Matthew F. Kalady ◽  
John C. Coffey
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Gene Expression Data ◽  
Late Stage ◽  
Disease Free Survival ◽  
Adverse Outcomes ◽  
Expression Data ◽  
Related Protein ◽  
Free Survival ◽  
Disease Free

508 Background: Substantial volumes of genetic expression data are archived within public gene expression repositories (PGER). Although the data contained is reported according to particular standards, it is not feasible to search the data using clinically relevant search terms (i.e., oncologic outcome). This study aimed to generate an archive of microarray expression data that could be searched using oncologically-relevant terminology, and then to test this facility. Methods: A UL Colorectal Cancer Archive was established based on data derived from the Gene Expression Omnibus (GEO). A software (Rover) was developed to permit clinically relevant searches using terminology such as stage and disease-free survival. As a first test, experiments were identified that compared early and late stage colorectal cancer. From these, consensus profiles were developed and adipocyte differentiation related protein identified as the top-most frequently dysregulated gene. As a second test, the cancer archive was again challenged to identify data sets annotated with outcome data. The association between ADFP and outcome was assessed using a regression-tree (CRT) based approach and Kaplan-Meier estimates. Results: The UL Colorectal cancer archive was constructed so as to permit the novice-user to search for gene expression data associated with particular clinical parameters. Rover was a graphic user interface that permitted these searches. ADFP was identified as dysregulated across the majority of experiments comparing early and late stage colorectal cancer. CRT-analyses identified levels of ADFP above which adverse outcomes were identified. In general, increasing ADFP was independently associated with adverse disease-free outcomes in stage II and III cancer. Conclusions: A novel archive of gene expression data was generated that (a) related to colorectal cancer and (b) could be searched using clinically-relevant terms. Using this archive ADFP was identified as dysregulated between early and late stage colorectal cancer. Increasing ADFP expression levels were associated with adverse disease-free survival in stages II and III colorectal cancer.

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