Circulating Methylated Septin 9 Nucleic Acid in the Plasma of Patients with Gastrointestinal Cancer in the Stomach and Colon

Lee, Hye Seung; Hwang, Sang Mee; Kim, Taek Soo; Kim, Duck-Woo; Park, Do Joong; Kang, Sung Bum; Kim, Hyung‐Ho; Park, Kyoung Un

doi:10.1593/tlo.13118

Cited by 71 publications

(87 citation statements)

References 27 publications

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“…The following 15 eligible studies then received full text evaluation and 1 of them was eliminated due to lack of relevance (26). Finally, 14 cohorts comprising 23 single studies were enrolled for the meta-analysis (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

Section: Resultsmentioning

confidence: 99%

“…Among the methylated genes in CRC, septin-9 has been highlighted as an ideal candidate biomarker (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Septin-9 was initially identified in myeloid neoplasia (20).…”

Section: Introductionmentioning

confidence: 99%

“…It acts as a suppressor gene in numerous cancer types (21,22). In previous years, an increasing number of studies have focused on the investigation of plasma methylated septin-9 for the detection of CRC (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Consequently, several types of assay kits regarding methylated septin-9 are being developed and have become commercial products.…”

Section: Introductionmentioning

confidence: 99%

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A pooled analysis of the diagnostic efficacy of plasmic methylated septin-9 as a novel biomarker for colorectal cancer

Zhang¹,

Zhang³

et al. 2017

Biomedical Reports

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Abstract. The methylation status of septin-9 gene in plasma has been developed as a promising biomarker to aid in the diagnosis of colorectal cancer (CRC). In this study, we aimed to evaluate the overall diagnostic ability of septin-9 methylation for detection of CRC. Studies on the diagnostic performance of plasma septin-9 in CRC were searched from the online databases up to January 31st, 2017. Risk of bias among the studies was estimated according to the Quality Assessment of Studies of Diagnostic Accuracy included in the Systematic Reviews (QUADAS) II checklist. The aggregation of the effect sizes was enabled by utilizing a bivariate analysis model. A meta-regression test and influence analysis were conducted to determine the underlying sources of heterogeneity. According to the predefined criteria, 1,462 patients with CRC from 14 eligible trials were included. The quantitative meta-analyses showed that methylated septin-9 in plasma sustained a pooled sensitivity of 0.67 (95% CI, 0.61-0.73) and specificity of 0.89 (95% CI, 0.86-0.92) in discriminating CRC patients from cancer-free individuals, along with an area under the curve of 0.87. Moreover, the stratified analyses grouped by ethnicity demonstrated that methylayted septin-9 testing achieved a better sensitivity of 0.72 (95% CI, 0.68-0.76) in the European-based population group and a higher specificity of 0.90 (95% CI, 0.88-0.92) in the Asian-based population group. Plasmic methylated septin-9 suggests a promising diagnostic efficacy in confirming CRC. However, more studies are required to confirm our findings.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A pooled analysis of the diagnostic efficacy of plasmic methylated septin-9 as a novel biomarker for colorectal cancer

Zhang¹,

Zhang³

et al. 2017

Biomedical Reports

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“…51,73,74 Promising results have also been reported using multigene methylation signatures for CRC screening in order to increase sensitivity and specificity. [61][62][63][64][65][66][67][68][69] For example, an approach using a BCAT1 and IKZF1 methylation assay identified approximately 70% of CRC. [75][76][77] Detection of tumor recurrence, minimal residual disease, and prognosis value Surgery alone cures a large fraction of patients with localized CRC.…”

Section: Cancer Diagnosis and Screeningmentioning

confidence: 99%

Future perspectives of circulating tumor DNA in colorectal cancer

et al. 2017

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Tumor biopsy is currently the gold standard for diagnosis and in determining cell signaling pathways involved in the development of treatment resistance. However, there are major challenges with this technique, including the need for serial sampling to monitor treatment resistance, which is invasive and also has the potential for selection bias due to intra-tumoral and inter-tumoral heterogeneity. These challenges highlight the need for more effective methods for obtaining Tumor samples. Liquid biopsy analyzes genetic material or tumor cells shed into the blood from the primary tumor and metastatic sites and consequently provides a comprehensive, real-time picture of the tumor burden in an individual patient. Indeed, liquid biopsy has the potential to revolutionize cancer management. Here, we review recent studies on the potential clinical applications of liquid biopsy using circulating tumor DNA in colorectal cancer, including screening, diagnosis, detection of minimal residual disease after surgery, detection of recurrence, prognosis, predicting treatment response, monitoring tumor burden or response during treatment, and tracking resistance. We also discuss recent data demonstrating the utility of detecting KRAS-mutated circulating tumor DNA, both at diagnosis to determine an appropriate treatment strategy and during anti-epidermal growth factor receptor therapy to predict treatment resistance. The future integration of liquid biopsy into clinical practice is discussed, together with alternative approaches and key questions that need to be answered in future clinical studies before this technology can be implemented and used routinely.

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“…However, the majority of these studies have focused on the total ccfDNA concentration in the blood or on the detection of genetic or epigenetic alterations (16)(17)(18)(19)(20). Moreover, the relationship between total ccfDNA concentration and outcome may be biased because an increase in the level of total ccfDNA might also be indicative of non-cancerous disease, such as inflammation or trauma (16).…”

Section: Introductionmentioning

confidence: 99%

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Messaoudi

Moulière

Manoir

et al. 2016

Clinical Cancer Research

147

108

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Purpose: Circulating cell-free DNA (ccfDNA) is a valuable source of tumor material obtained from a simple blood sampling that enables noninvasive analysis of the tumor genome. Our goal was to carry out a multiparametric analysis of ccfDNA and evaluate its prognostic value by investigating the overall survival (OS) of 97 metastatic colorectal cancer patients (mCRC).Experimental Design: Qualitative parameters (determination of the main KRAS exon2 and BRAF V600E mutations) and quantitative parameters (total ccfDNA concentration, mutant ccfDNA concentration, the proportion of mutant ccfDNA, and ccfDNA integrity index) were determined simultaneously in a single run using a unique Q-PCR multimarker approach (100% success rate).Results: The median follow-up time was 36 months and median OS was 22 months. Patients showing high ccfDNA levels had significantly shorter OS (18.07 months vs. 28.5 months, P ¼ 0.0087). Moreover, multivariate analysis revealed that a high ccfDNA level is an independent prognostic factor (P ¼ 0.034). All ccfDNA parameters were of prognostic interest: patients with higher levels of mutant ccfDNA and higher mutation loads for the detected mutations had shorter OS (P ¼ 0.0089 and P ¼ 0.05, respectively). In addition, the level of ccfDNA fragmentation correlated positively with decreased OS in the exclusive KRAS/ BRAF-mutant cohort of patients (P ¼ 0.0052) and appeared as a strong independent prognostic factor (P ¼ 0.0072), whereas it was not significant in the exclusive KRAS/BRAF WT cohort of patients (P ¼ 0.67).Conclusions: Our data provide for the first time qualitative and quantitative evidence in favor of multiparametric ccfDNA analysis in mCRC patients for prognostic assessment.

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Circulating Methylated Septin 9 Nucleic Acid in the Plasma of Patients with Gastrointestinal Cancer in the Stomach and Colon

Abstract: Considering the high incidence of plasma mSEPT9 in intestinal or mixed type GCs similar to CRCs, GC should be examined through the plasma mSEPT9 screening test. In addition, plasma mSEPT9 is proposed as a follow-up marker in CRC patients, but further validation is required.

Cited by 71 publications

References 27 publications

A pooled analysis of the diagnostic efficacy of plasmic methylated septin-9 as a novel biomarker for colorectal cancer

A pooled analysis of the diagnostic efficacy of plasmic methylated septin-9 as a novel biomarker for colorectal cancer

Future perspectives of circulating tumor DNA in colorectal cancer

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

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