Loss of KCNQ1 expression in stage II and stage III colon cancer is a strong prognostic factor for disease recurrence

Uil, Sjoerd H. den; Coupé, Veerle M.H.; Linnekamp, Janneke F.; Broek, Egon van den; Goos, Jeroen; Diemen, Pien M. Delis-van; Belt, Eric; Grieken, Nicole C.T. van; Scott, Patricia M.; Vermeulen, Louis; Medema, Jan Paul; Bril, Herman; Stockmann, H. B. A. C.; Cormier, Robert T.; Meijer, Gerrit A.; Fijneman, Remond J.A.

doi:10.1038/bjc.2016.376

Cited by 33 publications

(33 citation statements)

References 55 publications

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“…In contrast, no direct association between hypomethylation and higher gene expression could be concluded in the CpG site cg23750514 located in the KCNQ1 gene. Contrary to our finding, that hypomethylation is associated with poor prognosis in patients with non-metastatic CRC, the loss of KCNQ1 mRNA and protein expression in stage II and III colon cancer has been proposed as a prognostic factor for poor disease-free survival 42. Additionally, another report showed that low expression of KCNQ1 protein was significantly associated with poor OS in patients with CRC with liver metastases after hepatic resection 43.…”

Section: Discussioncontrasting

confidence: 99%

Genome-wide DNA methylation analysis reveals a prognostic classifier for non-metastatic colorectal cancer (ProMCol classifier)

Gündert

Edelmann

Benner

et al. 2017

Gut

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Section: Discussioncontrasting

confidence: 99%

Genome-wide DNA methylation analysis reveals a prognostic classifier for non-metastatic colorectal cancer (ProMCol classifier)

Gündert

Edelmann

Benner

et al. 2017

Gut

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“…For example, genetic variation in ion channels and pumps that are involved in potassium homeostasis may also be associated with genes that have a role in cell proliferations and differentiation. The SCNN1B gene is associated with serum potassium 26 as well as gastric cancer 9 and the KCNQ1 gene, which provides information for potassium channels, 27 is also associated with the risk of colon, 28 colorectal, 29 and pancreatic cancer. 30 Also, a polymorphism in the KCNJ4 gene, which encodes another potassium channel, is associated with prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

<p>Fasting Serum Levels of Potassium and Sodium in Relation to Long-Term Risk of Cancer in Healthy Men</p>

Falk¹,

Heir²,

Robsahm³

et al. 2020

CLEP

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Purpose: To examine whether serum levels of potassium and sodium were associated with long-term cancer risk in initially healthy men. Patients and Methods: A cohort of 1994 initially healthy men with no use of medication, aged 40-59 years, was followed for cancer during 40 years of follow-up. Associations between fasting electrolyte levels and cancer risk were assessed with incidence rates and Cox proportional hazards models. Results: Potassium, but not sodium, was linearly associated with cancer risk. This association remained significant after adjustment of several potential confounding factors, and also after excluding the first 10 years of follow-up. The age-adjusted risk of all-site cancer increased with 16% for each SD increase in potassium level. Men with hyperkalemia showed an incidence rate that was 40% higher than for men with normal potassium levels. Conclusion: Fasting serum potassium level in healthy men was positively associated with long-term cancer risk. Potassium or potassium ion channels may have a role in cell proliferation or differentiation. These findings might imply future cancer strategies for targeting individuals with high serum potassium levels.

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“…KCNQ1 is another tumor suppressor gene, and loss of its expression is considered to be an indicator of metastasis and poor prognosis [61–63]. There is also evidence that the reduction in KCNQ1 expression in cancer cells may be mediated by promoter hypermethylation [62, 64].…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Study of Leukocyte DNA Methylation and Biomarkers for Cancer Risk in Older Adults

Bartlett

Liang

Sandoval-Sierra

et al. 2019

Preprint

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19Background: Changes in DNA methylation over the course of life may provide 20 an indicator of risk for cancer. We explored longitudinal changes in CpG 21 methylation from blood leukocytes, and likelihood of a future cancer diagnosis. 22Methods: Peripheral blood samples were obtained at baseline and at follow-up 23 visit from 20 participants in the Health, Aging and Body Composition prospective 24 cohort study. Genome-wide CpG methylation was assayed using the Illumina 25 Infinium Human MethylationEPIC (HM850K) microarray. Results: Global 26 patterns in DNA methylation from CpG-based analyses showed extensive 27 changes in cell composition over time in participants who developed cancer. By 28 visit year 6, the proportion of CD8+ T-cells decreased (p-value = 0.02), while 29 granulocytes cell levels increased (p-value = 0.04) among participants diagnosed 30 with cancer compared to those who remained cancer-free (cancer-free vs. 31 cancer-present: 0.03 ± 0.02 vs. 0.003 ± 0.005 for CD8+ T-cells; 0.52 ± 0.14 vs. 32 0.66 ± 0.09 for granulocytes). Epigenome-wide analysis identified three CpGs 33 with suggestive p-values ≤ 10 -5 for differential methylation between cancer-free 34 and cancer-present groups, including a CpG located in MTA3, a gene linked with 35 metastasis. At a lenient statistical threshold (p-value ≤ 3 x 10 -5 ), the top 10 36 cancer-associated CpGs included a site near RPTOR that is involved in the 37 mTOR pathway, and the candidate tumor suppressor genes REC8, KCNQ1, and 38 ZSWIM5. However, only the CpG in RPTOR (cg08129331) was replicated in an 39 independent data set. Analysis of within-individual change from baseline to Year 40 6 found significant correlations between the rates of change in methylation in 41 RPTOR, REC8 and ZSWIM5, and time to cancer diagnosis. Conclusion: The 42 results show that changes in cellular composition explains much of the cross-43 sectional and longitudinal variation in CpG methylation. Additionally, differential 44 methylation and longitudinal dynamics at specific CpGs could provide powerful 45 indicators of cancer development and/or progression. In particular, we highlight 46CpG methylation in the RPTOR gene as a potential biomarker of cancer that 47 awaits further validation. 48 DNA methylation plays a central role in cell differentiation and in defining cellular 60 phenotypes. Differences in DNA methylation have been associated with a 61 growing list of morbidities, ranging from metabolic disorders and age-related 62 decline in health, to developmental and neuropsychiatric conditions. The 63 standard approach in an epigenome-wide association study (EWAS), which 64 attempts to link DNA methylation to disease, involves collection of a single 65 biospecimen from each participant (typically peripheral blood or saliva) and 66 performing cross-sectional analyses to compare methylation patterns in cases 67 against matched healthy controls [1, 2]. While differences in CpG methylation 68 between cases and controls may be directly related to disease, these case-69 control diff...

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Loss of KCNQ1 expression in stage II and stage III colon cancer is a strong prognostic factor for disease recurrence

Cited by 33 publications

References 55 publications

Genome-wide DNA methylation analysis reveals a prognostic classifier for non-metastatic colorectal cancer (ProMCol classifier)

Genome-wide DNA methylation analysis reveals a prognostic classifier for non-metastatic colorectal cancer (ProMCol classifier)

<p>Fasting Serum Levels of Potassium and Sodium in Relation to Long-Term Risk of Cancer in Healthy Men</p>

Longitudinal Study of Leukocyte DNA Methylation and Biomarkers for Cancer Risk in Older Adults

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