scholarly journals Tumor LINE-1 methylation level and colorectal cancer location in relation to patient survival

Oncotarget ◽  
2016 ◽  
Vol 7 (34) ◽  
pp. 55098-55109 ◽  
Author(s):  
Kosuke Mima ◽  
Jonathan A. Nowak ◽  
Zhi Rong Qian ◽  
Yin Cao ◽  
Mingyang Song ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Methylation Level ◽  
Patient Survival ◽  
Tumor Line

scholarly journals Prospective Study of Family History and Colorectal Cancer Risk by Tumor LINE-1 Methylation Level

2012 ◽  
Vol 105 (2) ◽  
pp. 130-140 ◽  
Author(s):  
Shuji Ogino ◽  
Reiko Nishihara ◽  
Paul Lochhead ◽  
Yu Imamura ◽  
Aya Kuchiba ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Prospective Study ◽  
Methylation Level ◽  
Colorectal Cancer Risk ◽  
Tumor Line

scholarly journals Tumor LINE-1 Methylation Level and Microsatellite Instability in Relation to Colorectal Cancer Prognosis

2014 ◽  
Vol 106 (9) ◽  
Author(s):  
Kentaro Inamura ◽  
Mai Yamauchi ◽  
Reiko Nishihara ◽  
Paul Lochhead ◽  
Zhi Rong Qian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Methylation Level ◽  
Cancer Prognosis ◽  
Tumor Line

scholarly journals Tumor Long Interspersed Nucleotide Element-1 (LINE-1) Hypomethylation in Relation to Age of Colorectal Cancer Diagnosis and Prognosis

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2016
Author(s):  
Naohiko Akimoto ◽  
Melissa Zhao ◽  
Tomotaka Ugai ◽  
Rong Zhong ◽  
Mai Chan Lau ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Diagnosis ◽  
Early Onset ◽  
Methylation Level ◽  
Linear Regression Analysis ◽  
Colorectal Cancers ◽  
Dna Hypomethylation ◽  
Tumor Line ◽  
Diagnosis And Prognosis

Evidence indicates the pathogenic role of epigenetic alterations in early-onset colorectal cancers diagnosed before age 50. However, features of colorectal cancers diagnosed at age 50–54 (hereafter referred to as “intermediate-onset”) remain less known. We hypothesized that tumor long interspersed nucleotide element-1 (LINE-1) hypomethylation might be increasingly more common with decreasing age of colorectal cancer diagnosis. In 1356 colorectal cancers, including 28 early-onset and 66 intermediate-onset cases, the tumor LINE-1 methylation level measured by bisulfite-PCR-pyrosequencing (scaled 0 to 100) showed a mean of 63.6 (standard deviation (SD) 10.1). The mean tumor LINE-1 methylation level decreased with decreasing age (mean 64.7 (SD 10.4) in age ≥70, 62.8 (SD 9.4) in age 55–69, 61.0 (SD 10.2) in age 50–54, and 58.9 (SD 12.0) in age <50; p < 0.0001). In linear regression analysis, the multivariable-adjusted β coefficient (95% confidence interval (CI)) (vs. age ≥70) was −1.38 (−2.47 to −0.30) for age 55–69, −2.82 (−5.29 to −0.34) for age 50–54, and −4.54 (−8.24 to −0.85) for age <50 (Ptrend = 0.0003). Multivariable-adjusted hazard ratios (95% CI) for LINE-1 methylation levels of ≤45, 45–55, and 55–65 (vs. >65) were 2.33 (1.49–3.64), 1.39 (1.05–1.85), and 1.29 (1.02–1.63), respectively (Ptrend = 0.0005). In conclusion, tumor LINE-1 hypomethylation is increasingly more common with decreasing age of colorectal cancer diagnosis, suggesting a role of global DNA hypomethylation in colorectal cancer arising in younger adults.

scholarly journals The loss of SHMT2 mediates 5-fluorouracil chemoresistance in colorectal cancer by upregulating autophagy

Oncogene ◽  
2021 ◽  
Author(s):  
Jian Chen ◽  
Risi Na ◽  
Chao Xiao ◽  
Xiao Wang ◽  
Yupeng Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Patient Survival ◽  
Serine Hydroxymethyltransferase ◽  
First Line ◽  
Xenograft Models ◽  
Potential Opportunity ◽  
First Line Treatment ◽  
Novel Therapeutic

Abstract5-Fluorouracil (5-FU)-based chemotherapy is the first-line treatment for colorectal cancer (CRC) but is hampered by chemoresistance. Despite its impact on patient survival, the mechanism underlying chemoresistance against 5-FU remains poorly understood. Here, we identified serine hydroxymethyltransferase-2 (SHMT2) as a critical regulator of 5-FU chemoresistance in CRC. SHMT2 inhibits autophagy by binding cytosolic p53 instead of metabolism. SHMT2 prevents cytosolic p53 degradation by inhibiting the binding of p53 and HDM2. Under 5-FU treatment, SHMT2 depletion promotes autophagy and inhibits apoptosis. Autophagy inhibitors decrease low SHMT2-induced 5-FU resistance in vitro and in vivo. Finally, the lethality of 5-FU treatment to CRC cells was enhanced by treatment with the autophagy inhibitor chloroquine in patient-derived and CRC cell xenograft models. Taken together, our findings indicate that autophagy induced by low SHMT2 levels mediates 5-FU resistance in CRC. These results reveal the SHMT2–p53 interaction as a novel therapeutic target and provide a potential opportunity to reduce chemoresistance.

Relationship between colorectal cancer glutathione levels and patient survival

2000 ◽  
Vol 43 (8) ◽  
pp. 1133-1140 ◽  
Author(s):  
Sam C. Barranco ◽  
Roger R. Perry ◽  
Mary E. Durm ◽  
Mohammed Quraishi ◽  
Alice L. Werner ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Patient Survival

The Clinical and Prognostic Significance of Protein Arginine Deiminases 2 and 4 in Colorectal Cancer

Pathobiology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Mohamed Gijon ◽  
Rachael L. Metheringham ◽  
Michael S. Toss ◽  
Samantha J. Paston ◽  
Lindy G. Durrant
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Survival Time ◽  
Patient Survival ◽  
Prognostic Significance ◽  
High Expression ◽  
Related Protein ◽  
Post Translational Modification

<b><i>Introduction:</i></b> Protein arginine deiminases (PADIs) are a family of enzymes that catalyse the post-translational modification of proteins. Association between PADI expression and clinicopathology, protein expression, and outcome was determined. <b><i>Methods:</i></b> PADI2 and PADI4 expression was assessed immunohistochemically in a cohort of colorectal cancer (CRC) patients. <b><i>Results:</i></b> CRC tissues expressed variable levels of PADI2 which was mainly localised in the cytoplasm and correlated with patient survival (<i>p</i> = 0.005); high expression increased survival time from 43.5 to 67.6 months. Expression of cytoplasmic PADI2 correlated with the expression of nuclear β catenin, PADI4, and alpha-enolase. In contrast, expression of nuclear PADI2 correlated with a decrease in survival (<i>p</i> = 0.010), with high expression decreasing survival from 76.4 to 42.9 months. CRC tissues expressed variable levels of PADI4 in both the nucleus and cytoplasm. Expression of cytoplasmic PADI4 correlated with survival (<i>p</i> = 0.001) with high expression increasing survival time from 48.1 to 71.8 months. Expression of cytoplasmic PADI4 correlated with expression of nuclear β catenin, alpha-enolase (<i>p</i> ≤ 0.0001, <i>p</i> = 0.002), and the apoptotic related protein, Bcl-2. Expression of nuclear PADI4 also correlated with survival (<i>p</i> = 0.011), with high expression of nuclear PADI4 increasing survival time from 55.4 to 74 months. Expression of nuclear PADI4 correlated with p53, alpha-enolase, and Bcl-2. Multivariate analysis showed that TNM stage, cytoplasmic PADI2, and PADI4 remained independent prognostic factors in CRC. Both PADI2 and PADI4 are good prognostic factors in CRC. <b><i>Conclusion:</i></b> High expression of cytoplasmic PADI2, PADI4, and nuclear PADI4 were associated with an increase in overall survival.

scholarly journals Improvement of Metastatic Colorectal Cancer Patient Survival: Single Institution Experience

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 369 ◽  
Author(s):  
Elisabetta Fenocchio ◽  
Federica Colombi ◽  
Maria Grazia Calella ◽  
Roberto Filippi ◽  
Ilaria Depetris ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Patient Survival ◽  
Colorectal Cancer Patient ◽  
Survival Rates ◽  
Integrated Approach ◽  
Metastatic Tumour ◽  
Single Institution ◽  
Significant Difference ◽  
Metastatic Colorectal Cancer Patient

The survival rates of patients with metastatic colorectal cancer (mCRC) have improved in recent years. We analysed the survival of mCRC patients followed at a single institution over the last 17 years. We retrospectively collected data from 899 mCRC patients treated from 2001 to 2016. Patients were divided into two groups based on the year of diagnosis: Cohort A (2001–2006) and Cohort B (2007–2014). A total of 788 patients were analysed. The median survival of the whole population was 32.0 months with a significant difference between Cohort A and B (29.2 vs. 33.5 months; p = 0.041). Surgical procedures significantly increased in Cohort B, however, no significant changes in survival were observed in patients undergoing surgery (58.9 months Cohort A vs. 58.2 months Cohort B, p = 0.822). Similarly, we did not demonstrate survival improvement in patients treated with systemic therapy alone (18.9 months Cohort A vs. 20.7 months Cohort B; p = 0.948). At the multivariate analysis, right-sided primary and synchronous metastatic tumour were found to be independent unfavorable prognostic factors. Improvements of mCRC patient survival might relate to integrated approach, with more patients undergoing extra-hepatic surgery. The medical approach seems to have had a more favourable impact on subgroups characterized by a worse prognosis.

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