Increased Tumor Ascorbate is Associated with Extended Disease-Free Survival and Decreased Hypoxia-Inducible Factor-1 Activation in Human Colorectal Cancer

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.

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Thymidylate synthase expression pattern, expression level and single nucleotide polymorphism are predictors for disease-free survival in patients of colorectal cancer treated with 5-fluorouracil

International Journal of Oncology ◽

10.3892/ijo.28.5.1303 ◽

2006 ◽

Author(s):

María-Encarnación Fernández-Contreras ◽

Sandra Sánchez-Prudencio ◽

José-Javier Sánchez-Hernández ◽

María-Luisa García de Paredes ◽

Javier Gisbert ◽

...

Keyword(s):

Colorectal Cancer ◽

Single Nucleotide Polymorphism ◽

Expression Pattern ◽

Thymidylate Synthase ◽

Disease Free Survival ◽

Expression Level ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Free Survival ◽

Disease Free

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

The American Surgeon ◽

10.1177/000313480607201007 ◽

2006 ◽

Vol 72 (10) ◽

pp. 875-879 ◽

Cited By ~ 8

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.

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Low radiographic muscle density is associated with lower overall and disease-free survival in early-stage colorectal cancer patients

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-018-2736-z ◽

2018 ◽

Vol 144 (11) ◽

pp. 2139-2147 ◽

Cited By ~ 8

Author(s):

Harm van Baar ◽

S. Beijer ◽

M. J. L. Bours ◽

M. P. Weijenberg ◽

M. van Zutphen ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Early Stage ◽

Disease Free Survival ◽

Free Survival ◽

Muscle Density ◽

Colorectal Cancer Patients ◽

Disease Free

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DPYD c.1905 + 1G>A Promotes Fluoropyrimidine-Induced Anemia, a Prognostic Factor in Disease-Free Survival, in Colorectal Cancer

Genetic Testing and Molecular Biomarkers ◽

10.1089/gtmb.2020.0285 ◽

2021 ◽

Vol 25 (4) ◽

pp. 276-283

Author(s):

Adem Deligonul ◽

Secil Aksoy ◽

Gulcin Tezcan ◽

Berrin Tunca ◽

Ozkan Kanat ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factor ◽

Disease Free Survival ◽

Free Survival ◽

Disease Free

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

Journal of International Medical Research ◽

10.1177/0300060518819620 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1829-1842 ◽

Cited By ~ 2

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.

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