Hypermethylation of the SEPT9 Gene Suggests Significantly Poor Prognosis in Cancer Patients: A Systematic Review and Meta-Analysis

Shen, Na; Wang, Ting; Li, Delei; Zhu, Yaowu; Xie, Hai; Lu, Yanjun

doi:10.3389/fgene.2019.00887

Cited by 11 publications

(11 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The mSEPT9 has been demonstrated to be an independent risk factor and can predict the long-term survival of both CRC and HCC. 9 , 30 , 31 In the present study, we demonstrated that this assay is an independent factor and predictive marker for long-term survival for all four types of digestive cancers. Predictions based on dichotomized pre-therapeutic mSEPT9 interpretation suggested that patients with digestive cancer who had undetectable levels of mSEPT9 in their blood prior to therapy would generally exhibit significantly better survival rates than those with detectable levels of mSEPT9 in their blood.…”

Section: Discussionsupporting

confidence: 64%

“…Indeed, this marker has been shown to be effective in a variety of applications for CRC, including the screening of average-risk populations, 1 opportunistic screening, 3 , 4 the monitoring of therapeutic effects in surgery, 30 the monitoring of therapeutic effects during late-stage CRC, 31 and the prediction of therapeutic effects and long-term survival in patients with CRC. 30 , 31 However, it should be noted that the prediction of survival by mSEPT9 was largely dependent on cancer stage, and that patients with advanced stages of cancer have higher levels of mSEPT9 in their blood; consequently, these patients are more likely to test positive and have a worse prognosis than those with early stages. Therefore, our stratification of survival by stage clearly showed that the marker may be predictable for the long-term survival of stage III–IV patients but not predictable for stage I–II patients under the current study design and follow-up duration.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Opportunistic screening and survival prediction of digestive cancers by the combination of blood mSEPT9 with protein markers

et al. 2020

View full text Add to dashboard Cite

Background: The early detection of digestive cancers and precancerous diseases remains a significant challenge. This study aimed to investigate the performance of the blood methylated SEPT9 ( mSEPT9) assay, and the combination of this assay with serum protein markers, in hospital-based opportunistic screening strategies for digestive cancers. Methods: Opportunistic screening was performed in the participating hospitals on outpatients and inpatients who met specific inclusion criteria. We recruited a total of 2030 subjects, including 764 cancer patients [291 colorectal cancer (CRC), 239 gastric cancer (GC), 106 esophageal cancer (EC), and 128 hepatocellular carcinoma (HCC)], 423 subjects with precancerous diseases, and 843 normal subjects. All samples were transported to an authenticated clinical laboratory where the mSEPT9 tests were performed. Results: When used separately, the mSEPT9 detected CRC, GC, EC, and HCC, with a sensitivity of 76.6% [area under the receiver operating characteristic curve (AUC) = 0.86)], 47.7% (AUC = 0.76), 42.6% (AUC = 0.69), and 76.7% (AUC = 0.85) and a specificity of 94.6%, 92.3%, 92.5%, and 87.7%, respectively. The mSEPT9 assay also had potent ability to discriminate cancer from non-cancer subjects. The combination of mSEPT9 with CEA, CA724, SNCG, or AFP significantly enhanced the sensitivity for CRC, GC, EC, and HCC to 86.4% (AUC = 0.99, specificity = 92.8%), 63.6% (AUC = 0.86, specificity = 91.1%), 71.3% (AUC = 0.81, specificity = 82.1%), and 83.3% (AUC = 0.93, specificity = 85.1%), respectively. The performance of the mSEPT9 assay was influenced by cancer stage, patient age, pathological types, and the location of cancer. We also identified that mSEPT9 was an independent risk factor and was a valuable predictor for the long-term survival of digestive cancer patients, with a hazard ratio of 2.84, 2.07, 1.88, and 2.45, for CRC, GC, EC, and HCC, respectively. Conclusion: The blood mSEPT9 assay, whether used alone or in combination with serum protein markers, is effective for the opportunistic screening of digestive cancers. Furthermore, mSEPT9 is an independent risk factor and a predictive marker for the long-term survival of digestive cancer patients.

show abstract

Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Opportunistic screening and survival prediction of digestive cancers by the combination of blood mSEPT9 with protein markers

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The pathological phenotype of rightsided colon cancer is poor differentiation, high proportion of advanced disease, increased mucinous adenocarcinoma, and high propensity for complications and second primary intestinal tumor that associates with poor prognosis (Missiaglia et al, 2014;Sveen et al, 2019). Further, a previous study observed differences in the positive rate of SEPT9 methylation in the peripheral blood of CRC patients with varied clinicopathological characteristics, and its positive rate is significantly related to the malignant biological behavior (Shen et al, 2019). Our previous studies showed that the methylation of SEPT9 is associated with the TNM stage, total tumor volume, and mismatch repair deficient status (Sun et al, 2019), suggesting that mSEPT9 in peripheral blood may be related with the pathological stage and the prognosis of patients.…”

Section: Discussionmentioning

confidence: 97%

“…However, the influence of CIMP on the drug efficacy is still unclear. At present, studies about mSEPT9 mainly focus on screening, diagnosis, prognosis, and correlation analysis with histopathology, and Shen N et al reported that the hypermethylation of SEPT9 associated with worse overall survival (OS) and disease-free survival (DFS) ( Shen et al, 2019 ), but there were no systematic reports about the relationship between mSEPT9 with specific molecular characteristics of CRC and the prognosis value of adjuvant chemotherapy or recurrence. Our previous study showed that mSEPT9 is related to the TNM stage, Dukes stage, and dMMR status of CRC ( Sun et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Screening and Prognostic Value of Methylated Septin9 and its Association With Clinicopathological and Molecular Characteristics in Colorectal Cancer

Sun

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

Screening of CRC continues to show poor compliance of endoscopy examination. The detection of mSEPT9 in peripheral blood is among the safe and simple early screening methods for CRC. The issue of how to elucidate whether detection of mSEPT9 in peripheral blood can effectively improve compliance of endoscopy and increase the early diagnosis rate of CRC and the relationship between levels of mSEPT9 in the peripheral blood and clinical stage, pathological classification, and expression of characteristic molecules in CRC remains unsolved. A total of 7759 individuals participated in the study that was performed using a questionnaire for screening of high-risk CRC. The endoscopic detection compliance of individuals with high-risk CRC who underwent the fecal occult blood test (FOBT) or mSEPT9 test was compared based on the results of the questionnaire. Additionally, correlation of mSEPT9 levels in the peripheral blood with clinicopathological features, mutation status of TP53, mismatch repair deficiency (dMMR), and KRAS/NRAS/BRAF/PIK3CA genotype was analyzed, and association of biomarkers with cancer-specific survival (CSS) and time to recurrence (TTR) was compared. We also detected levels of mSEPT9 in the peripheral blood of patients with CRC 7 days after surgery and compared the prognostic value of mSEPT9 with CEA. Results of our study showed that the mSEPT9 test could improve compliance of endoscopy and indicated a higher percentage of patients with positive mSEPT9 willing to undergo endoscopy detection than in those with positive FOBT. The specificity and sensitivity of mSEPT9 were better than that of FOBT for the detection of CRC. mSEPT9 was associated with the TNM stage, dMMR, and mutations in TP53, BRAF, and PIK3CA. A Ct value of mSEPT9 ≤ 37.5 was significantly related to poor CSS. mSEPT9 could affect association of dMMR and BRAF and PIK3CA mutations with CSS in a specific stage of CRC. The positive rate of mSEPT9 after surgery was found to correlate with poor TTR, and sensitivity was higher than CEA. The combination of mSEPT9 with CEA had a better prognostic value than that of mSEPT9 alone. The level of mSEPT9 was related to dMMR, mutations in TP53, BRAF, and PIK3CA, and was an effective biomarker for the prognosis of patients with CRC.

show abstract

“…ЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИ ТОМ 6 / VOL. 6 желудка, предстательной железы, вне-и внутрипеченочных желчных протоков [11].…”

Section: Al Identification Of a New Methylation Site In The Sept9 Prunclassified

Identification of a new methylation site in the Sept9 promoter region for the diagnosis of hepatocellular carcinoma

et al. 2019

View full text Add to dashboard Cite

Background. Over 600,000 people die from hepatocellular carcinoma (HCC) each year worldwide. The disease is often detected at advanced stages and in many cases is not curable. Early diagnostic and monitoring of HCC recurrences remains a substantial problem in clinical oncology. That determines the need for a search for highly sensitive and specific biomarkers for the non-invasive of HCC diagnostics. The objective of the study. Identification of the hypermethylated locus in the promoter region of the septin 9 (Sept9) gene based on the annotated methylomes from the public databases. Experimental validation of methylation on a pilot panel of paired clinical samples of patients with HCC, as well as tissue samples from patients with benign liver tumors and lymphocytes from healthy donors. Materials and methods. To analyze the methyl data, samples of HCC from TCGA, hepatocellular adenoma from GEO (Gene Expression Omnibus) depository, peripheral blood cells and tissues of healthy donors from Methbank were used. Experimental validation of methylation levels of the identified site was carried out on a pilot panel of clinical samples by bisulphite pyrosequencing using PyroMark Q24.Results. Based on the analysis of methylome data, we selected cg20275528 site, which is characterized by high level of methylation in HCC tissues and minimal levels of methylation in non-tumor liver tissue, hepatocellular adenoma and peripheral blood of healthy donors. Experimental testing on a pilot panel of clinical specimens showed that the level of marker site methylation in HCC (42 % median) is significantly higher than in non-tumor liver tissues (3 % median) and benign neoplasms (1.5 % median) and exceeds the threshold value in HCC compared to paired samples of adjacent non-tumor liver tissue in 20 out of 30 studied cases (66.6 %). The general possibility for cg20275528 methylation detection in circulating DNA of plasma in HCC patients was shown.Conclusion. The obtained results indicate that the approach to the detection and experimental verification of diagnostically significant markers developed and tested in this study can be used to identify new differentially methylated sites and to establish new approaches for non-invasive HCC diagnosis.

show abstract

Hypermethylation of the SEPT9 Gene Suggests Significantly Poor Prognosis in Cancer Patients: A Systematic Review and Meta-Analysis

Cited by 11 publications

References 35 publications

Opportunistic screening and survival prediction of digestive cancers by the combination of blood mSEPT9 with protein markers

Opportunistic screening and survival prediction of digestive cancers by the combination of blood mSEPT9 with protein markers

Screening and Prognostic Value of Methylated Septin9 and its Association With Clinicopathological and Molecular Characteristics in Colorectal Cancer

Identification of a new methylation site in the Sept9 promoter region for the diagnosis of hepatocellular carcinoma

Contact Info

Product

Resources

About