The SEPT9 gene methylation assay is the first FDA-approved blood assay for colorectal cancer (CRC) screening. Fecal immunochemical test (FIT), FIT-DNA test and CEA assay are also in vitro diagnostic (IVD) tests used in CRC screening. This meta-analysis aims to review the SEPT9 assay performance and compare it with other IVD CRC screening tests. By searching the Ovid MEDLINE, EMBASE, CBMdisc and CJFD database, 25 out of 180 studies were identified to report the SEPT9 assay performance. 2613 CRC cases and 6030 controls were included, and sensitivity and specificity were used to evaluate its performance at various algorithms. 1/3 algorithm exhibited the best sensitivity while 2/3 and 1/1 algorithm exhibited the best balance between sensitivity and specificity. The performance of the blood SEPT9 assay is superior to that of the serum protein markers and the FIT test in symptomatic population, while appeared to be less potent than FIT and FIT-DNA tests in asymptomatic population. In conclusion, 1/3 algorithm is recommended for CRC screening, and 2/3 or 1/1 algorithms are suitable for early detection for diagnostic purpose. The SEPT9 assay exhibited better performance in symptomatic population than in asymptomatic population.

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The performance of the SEPT9 gene methylation assay and a comparison with other CRC screening tests: A meta-analysis.

Diagnostic Accuracy of Methylated SEPT9 for Blood-based Colorectal Cancer Detection: A Systematic Review and Meta-Analysis

Diagnostic Accuracy of Methylated SEPT9 for Blood-based Colorectal Cancer Detection: A Systematic Review and Meta-Analysis.

Colorectal cancer (CRC) is still a leading cause of cancer death worldwide. Less than half of cases are diagnosed when the cancer is locally advanced. CRC is a heterogenous disease associated with a number of genetic or somatic mutations. Diagnostic markers are used for risk stratification and early detection, which might prolong overall survival. Nowadays, the widespread use of semi-invasive endoscopic methods and feacal blood tests characterised by suboptimal accuracy of diagnostic results has led to the detection of cases at later stages. New molecular noninvasive tests based on the detection of CRC alterations seem to be more sensitive and specific then the current methods. Therefore, research aiming at identifying molecular markers, such as DNA, RNA and proteins, would improve survival rates and contribute to the development of personalized medicine. The identification of “ideal” diagnostic biomarkers, having high sensitivity and specificity, being safe, cheap and easy to measure, remains a challenge. The purpose of this review is to discuss recent advances in novel diagnostic biomarkers for tumor tissue, blood and stool samples in CRC patients.

https://www.mdpi.com/1422-0067/23/2/852/pdf?version=1642147067

Novel Diagnostic Biomarkers in Colorectal Cancer

Background The applications of the SEPT9 assay are expanding from CRC early diagnosis to screening, therapeutic effect monitoring and prognosis prediction. Its performance in these areas has not been thoroughly examined. Objective We aim to evaluate the performance of the SEPT9 assay in CRC screening, diagnosis and therapy by reviewing the current data published in these aspects. Methods The Ovid MEDLINE, EMBASE, CBMdisc (China Biology Medicine disc) and CJFD (Chinese Journal Full - text Database) database were searched for potential reports on the assay performance. Letters, reviews, meta-analysis and guidelines, basic research studies and articles irrelevant to mSEPT9 detection assays were excluded. Finally, data from 19 studies was summarized and systematically reviewed to clarify the assay performance. Results 2/3 algorithm provided the best overall performance in diagnosis and screening, while the 1/3 algorithm exhibited the best sensitivity in screening. The combination of SEPT9 assay with FIT and/or CEA enhanced the CRC detection rate in screening. The SEPT9 assay appeared to be effective in monitoring the therapeutic effect and may potentially predict the CRC recurrence and survival. Conclusion The SEPT9 assay exhibited satisfactory performance in CRC diagnosis and screening, while more evidence is needed for therapeutic effect monitoring and prognosis prediction.

A systematic review of the performance of the SEPT9 gene methylation assay in colorectal cancer screening, monitoring, diagnosis and prognosis.

DNA hypermethylation in blood is becoming an attractive candidate marker for colorectal cancer (CRC) detection. To assess the diagnostic accuracy of blood hypermethylation markers for CRC in different clinical settings, we conducted a meta-analysis of published reports. Of 485 publications obtained in the initial literature search, 39 studies were included in the meta-analysis. Hypermethylation markers in peripheral blood showed a high degree of accuracy for the detection of CRC. The summary sensitivity was 0.62 [95% confidence interval (CI), 0.56–0.67] and specificity was 0.91 (95% CI, 0.89–0.93). Subgroup analysis showed significantly greater sensitivity for the methylated Septin 9 gene (SEPT9) subgroup (0.75; 95% CI, 0.67–0.81) than for the non-methylated SEPT9 subgroup (0.58; 95% CI, 0.52–0.64). Sensitivity and specificity were not affected significantly by target gene number, CRC staging, study region, or methylation analysis method. These findings show that hypermethylation markers in blood are highly sensitive and specific for CRC detection, with methylated SEPT9 being particularly robust. The diagnostic performance of hypermethylation markers, which have varied across different studies, can be improved by marker optimization. Future research should examine variation in diagnostic accuracy according to non-neoplastic factors.

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Diagnostic Performance of DNA Hypermethylation Markers in Peripheral Blood for the Detection of Colorectal Cancer: A Meta-Analysis and Systematic Review

Objective
To explore the role of detecting the methylation status of gene Septin9 (SEPT9) in plasma for colorectal cancer screening in Chinese population.


Methods
Patients were collected from Beijing Military General Hospital since September 2013 to February 2014. The performance of SEPT9 assay was validated in a single-blind study of 80 cases with colonoscopy and pathologically verified colorectal cancer and 52 normal controls. The detection of Septin9 gene methylation in peripheral blood was performed by fluorescence quantitative polymerase chain reaction (PCR). And immunoassay fecal occult blood test was conducted to compare the superiority of methylated Septin9 for screening colorectal cancer.


Results
The Septin9 assay successfully identified 75.0%(95%CI: 64.7%-83.6%) of cancers at a specificity of 98.1%(95%CI: 90.9%-99.9%). And it was superior to fecal occult blood screening for colorectal cancer (sensitivity 79.5% vs 53.8%, P<0.05).


Conclusion
Determination of SEPT9 methylation status is an innovative non-invasive plasma screening test for colorectal cancer.


Key words: 
Colorectal neoplasms; DNA methylation; Genes, Septin9

Significance of Septin9 gene methylation detection of plasma circulation DNA in colorectal cancer screening

Objective To investigate the characteristics of APC gene germline mutation in Chinese patients with familial adenomatous polyposis ( FAP). Methods The genomic DNA was extracted from peripheral venous blood drawn from probands of 14 Chinese FAP families from Beijing, Hebei, Henan,Anhui, Inner Mongolia, Shanxi and Fujian. The APC gene was amplified by PCR and underwent direct sequencing. Large fragment deletion was detected by multiplex ligation-dependent probe amplification (MLPA) only in micromutation-negative samples found by sequencing. Results APC gene micromutations were found in 9 probands and the mieromutation detection rate was 64. 3%, including 6 frameshift mutations, 2 splicing mutations and 1 nonsense mutation. Large fragment deletions of APC gene were detected in 2 probands ( 14. 3% ). The total mutation detection rate of micromutation and large fragment deletion was 78. 6%. Four novel micmromutations and 2 novel large fragment deletions were found, including c. 2336-2337insT, c. 3923-3929delAAGAAAA, c. 532-2A>T, c. 4179-4180GAdelinsT, large fragment deletions of exons 11 and 10A and large fragment deletion of exon 15 start. Conclusions In Chinese FAP patients, the germline mutation type of APC gene is variable; the majority is of frameshift mutation. The most common mutation site is exon 15. The mutation detection rate of APC gene can be boosted effectively by direct sequencing in combination with MLPA.

Key words: 
Adenomatous pelyposis coli; Genes, APC; Mutation; Gene deletion; Gene amplification

[Detection of APC gene germline mutation in Chinese familial adenomatous polyposis by direct sequencing in combination with multiplex ligation-dependent probe amplification].

Objective
To explore the Helicobacter pylori(Hp) infection rate among army and navy recruits, examine its associated risk factors and provide theoretic rationales for Hp control.


Methods
A cross-sectionalstudy was performed for 1 732 subjects (aged 17-24 years) selected from 18 new recruit populations in Inner Mongolia and Zhoushan area from September 2013 to November 2013. Hp infection was detected by 13C-urea breath test. Meanwhile, a questionnaire containing 62 potential factors related to Hp infection was surveyed. In addition, 13C-urea breath test was performed in 513 navy veterans (aged 19-51 years) in Zhoushan area from April 2013 to October 2013. The data of risk factors were analyzed by χ2 test and multivariate Logistic regression.


Results
A total of 2 162 soldiers were enrolled and 1 649 new recruits completed two surveys. The overall Hp infection rate was 46.5%(768/1 649), which is lower than the previous studies (52.9%). And it was 47.0%(377/802) in army new recruits and 46.0%(390/847) in navy new recruits. For new recruits, Hp infection was associated with number of family members, washing tableware with detergents, first drinking age and paring fruits before eating (all P 0.05). The Hp infection rate was higher in recruits from the West China and North China. In addition, the infection rate was 60.8%(312/513) in a population of 513 veterans. It was 46.6%(768/1 649) in recruits less than onemonth of service, 59.2%(180/304) in recruits less than two years of service and 63.2%(132/209) in recruits more than two years of service, the difference had statistical significance (P<0.05). Logistic analysis of multiple variables showed that number of family members, washing tableware with detergents, first drinking age and paring fruits before eating were independent risk factors (OR=1.574, 0.538, 0.638, 0.855; 95%CI: 1.077-2.301, 0.362-0.798, 0.486-0.837, 0.457-0.961).


Conclusions
The Hp infection rate is similar between army and navy recruits. It has dropped significantly and its epidemic region changed in new male recruits compared to a decade ago in china. Hp infection clustered within families. The factors including fewer family members, washing tableware without detergents, first drinking at young age and no paring fruits before eating are risk factors of Hpinfection. And a longer service time is associated with higher Hp infection rate in recruits.


Key words: 
Helicobacter pylori; Risk factors; Cross-sectional studies

Hejuan An

Papers

Significance of Septin9 gene methylation detection of plasma circulation DNA in colorectal cancer screening

[Detection of APC gene germline mutation in Chinese familial adenomatous polyposis by direct sequencing in combination with multiplex ligation-dependent probe amplification].

Risk factors associated with Helicobacter pylori infection in army and navy recruits

Clinicopathological features of non-familial colorectal cancer with high-frequency microsatellite instability.