DNA methylation biomarkers in stool for early screening of colorectal cancer

Chen, Jie; Sun, Haipeng; Tang, Weili; Zhou, Lin; Xie, Xiaoqing; Qu, Zhan; Chen, Mengfei; Wang, Shunyao; Yang, Ting; Dai, Ying; Wang, Yongli; Gao, Tangjie; Zhou, Qiao; Song, Zhuo; Liao, Mingmei; Liu, Weidong

doi:10.7150/jca.34944

Cited by 49 publications

(37 citation statements)

References 33 publications

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“…Our earlier work on another blood based CRC screening assay, ColoDefense test that combines the detection of SEPT9 and SDC2 methylation in a single qPCR reaction, also improved the detection rates for early stage CRC and AA (Chen Y. et al, 2019;Zhao et al, 2019). To our knowledge, there has been only one published study examining the performance of methylated SEPT9 in combination with other methylation biomarkers on stool samples, and the AUC of methylated SEPT9 in that study was 0.815 (Chen J. et al, 2019). However, the performance of single methylated SEPT9 test on stool samples for each CRC stage and the performance comparison between stool methylated SEPT9 test and plasma methylated SEPT9 test have never been reported.…”

Section: Discussionmentioning

confidence: 99%

Performance Comparison Between Plasma and Stool Methylated SEPT9 Tests for Detecting Colorectal Cancer

et al. 2020

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Colorectal cancer (CRC) is the most common type of malignancies of the gastrointestinal tract worldwide. Plasma methylated SEPT9 test has been used clinically for CRC screening for several years, but the study about the performance comparison between plasma and stool has rarely been reported. In this study, 124 plasma samples, 100 stool samples, and 60 sets of plasma and paired stool samples were collected and tested by a methylated SEPT9 test in three PCR replicates. The results indicated methylated SEPT9 levels in stool samples were significant higher than those in plasma samples (p < 0.0001). When a plasma sample was called positive if 1 out of 3 PCR replicates was positive and a stool sample was called positive if 3 out of 3 PCR replicates were positive with a mean Cp value of less than 40.0, stool methylated SEPT9 test achieved similar sensitivity (83.3% vs 85.6%) and specificity (92.1% vs 90.1%) to those by plasma methylated SEPT9 test, and the overall concordance rate is 78.3%. However, stool methylated SEPT9 test showed 35.9 and 7.9% improvement in detecting advanced adenomas (AA) and stage I-II CRC in comparison to plasma methylated SEPT9 test. The AUC for plasma methylated SEPT9 and stool methylated SEPT9 in detecting CRC were 0.885 (95% CI: 0.832-0.938) and 0.935 (95% CI: 0.895-0.975), respectively. In conclusion, stool methylated SEPT9 test showed higher sensitivities for detection AA and early stage CRC compared with plasma methylated SEPT9 test, and stool methylated SEPT9 test may be a more suitable tool for early stage CRC screening.

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Section: Discussionmentioning

confidence: 99%

Performance Comparison Between Plasma and Stool Methylated SEPT9 Tests for Detecting Colorectal Cancer

et al. 2020

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“…LncRNA promoter present a global hyper-methylation character in colon cancer some studies have point out DNA methylation have potential role in early screening of colon cancer [31]. Here, we investigate the DNA methylation character in lncRNA promoter for colon cancer.…”

Section: Resultsmentioning

confidence: 95%

Dissecting drug and prognostic lncRNA signature mediated by DNA methylation and transcription factor in colon cancer

Zhang¹,

Shen²,

Song³

et al. 2020

Preprint

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Background: Colon cancer is still the most commonly diagnosed malignancy and leading cause of death worldwide. Apart from living habits, genetic and epigenetic changes are key factors to influence the risk of colon cancer. However, the impact of epigenetic alterations in non-coding RNAs and the consequences for colon cancer has not been fully characterized.Methods: We detected differential methylation sites (DMSs) in lncRNA promoters, and identified lncQTMs by association test. To investigate TF binding affected by DNA methylation, we characterized known TF motif occurrence among DMSs collected from MEME suit. We further combined methylome and transcriptome data to construct TF-methylation-lncRNA relationships. To study the role of lncRNAs in drug response, we used pharmacological and lncRNA profiles derived from CCLE and predict drug response by lncRNA expression level. We also used the combination of TF-methylation-lncRNA relationship to stratified patient survival information by a risk model.Results: DNA methylation display global hyper-methylation character in lncRNA promoters, and they tend to have negative relationship with the corresponding lncRNAs. Negative lncQTMs located near TSS have more significant and stronger correlation with the corresponding lncRNAs. Some lncRNAs mediated by the interplay between DNA methylation and TFs are proved markers for colon cancer. Typically, lncRNA CAHM, RP11-834C11.4 and LINC00460 are good predictors for 5 drug components (17-AAG, Sorafenib, TKI258, RAF265, Topotecan) in colon cancer. And we found HES1_cg24685006_RP4-728D4.2 and SREBF1_cg05372727_LINC00460 relationships are prognostic signatures for colon cancer.Conclusions: These findings suggested lncRNAs mediated by the interplay between DNA methylation and TFs are promising predictors for drug response, besides, combined TF-methylation-lncRNA can serve as prognostic signature for colon cancer.

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“…Alteration of DNA methylation has been implicated in tumor progression and disease development, and studies have identified a potential role for DNA methylation in early screening of colon cancer ( Chen et al, 2019 ). Here, we investigated DNA methylation in lncRNA promoters in colon cancer.…”

Section: Resultsmentioning

confidence: 99%

Drug Response Associated With and Prognostic lncRNAs Mediated by DNA Methylation and Transcription Factors in Colon Cancer

et al. 2020

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Colon cancer is the most commonly diagnosed malignancy and the leading cause of cancer deaths worldwide. As well as lifestyle, genetic and epigenetic changes are key factors that influence the risk of colon cancer. However, the impact of epigenetic alterations in non-coding RNAs and their consequences in colon cancer have not been fully characterized. We detected differential methylation sites (DMSs) in long non-coding RNA (lncRNA) promoters and identified lncRNA expression quantitative trait methylations (lncQTMs) by association tests. To investigate how transcription factor (TF) binding was affected by DNA methylation, we characterized the occurrence of known TFs among DMSs collected from the MEME suite. We further combined methylome and transcriptome data to construct TF–methylation–lncRNA relationships. To study the role of lncRNAs in drug response, we used pharmacological and lncRNA profiles from the Cancer Cell Line Encyclopedia (CCLE) and investigated the association between lncRNAs and drug activity. We also used combinations of TF–methylation–lncRNA relationships to stratify patient survival using a risk model. DNA methylation sites displayed global hyper-methylation in lncRNA promoters and tended to have negative relationships with the corresponding lncRNAs. Negative lncQTMs located near transcription start sites (TSSs) had more significant correlations with the corresponding lncRNAs. Some lncRNAs found to be mediated by the interplay between DNA methylation and TFs were previously identified as markers for colon cancer. We also found that the ELF1-cg05372727- LINC00460 relationship were prognostic signatures for colon cancer. These findings suggest that lncRNAs mediated by the interplay between DNA methylation and TFs are promising predictors of drug response, and that combined TF–methylation–lncRNA can serve as a prognostic signature for colon cancer.

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DNA methylation biomarkers in stool for early screening of colorectal cancer

Cited by 49 publications

References 33 publications

Performance Comparison Between Plasma and Stool Methylated SEPT9 Tests for Detecting Colorectal Cancer

Performance Comparison Between Plasma and Stool Methylated SEPT9 Tests for Detecting Colorectal Cancer

Dissecting drug and prognostic lncRNA signature mediated by DNA methylation and transcription factor in colon cancer

Drug Response Associated With and Prognostic lncRNAs Mediated by DNA Methylation and Transcription Factors in Colon Cancer

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