We developed and validated a microsimulation model to assess the effectiveness of colonoscopy (COL), flexible sigmoidoscopy (FS), high-sensitivity guaiac fecal occult blood-test (HS-gFOBT), fecal immunochemical test (FIT), multitarget stool DNA test (FIT-DNA), computed tomography colonography (CTC), and methylated SEPT9 DNA test (SEPT9) in terms of CRC incidence and mortality, incremental life years gained (LYG), number of colonoscopies, and adverse events for men and women 50 years or older over their lifetime.
Seventy-three percent of CRC patients were <sup>m</sup>SEPT9-positive at 94.5% specificity, and 17.1% of patients with intestinal polyps and adenoma were <sup>m</sup>SEPT9-positive at 94.5% specificity, which were higher than FOBT for the screening of CRC.
In comparison with healthy subjects, the pooled sensitivity with 95% confidence intervals (CIs) of SEPT9 methylation for the diagnosis of CRC was 0.74 (95% CI: 0.61-0.84) in the 1/3 algorithm group, whereas the specificity was 0.96 (95% CI: 0.95-0.97) in the 2/3 algorithm group.
<i>TP53, KRAS, APC</i>) has limited diagnostic sensitivity (40-60%), however, methylated DNA including <i>SEPT9, SFRP1, SDC2</i> can be applied with higher sensitivity (up to 90%) for CRC.Circulating miRNAs (e.g. miR-21, miR-92, miR-141) provide comparably high sensitivity for CRC as the circulating tumor cell mRNA markers (e.g.EGFR, CK19, CK20, CEA).
Apart from SEPT9, other methylated biomarkers including tachykinin-1 (TAC1), somatostatin (SST), and runt-related transcription factor 3 (RUNX3) have been shown to effectively detect CRC in a multitude of sample types.
This includes a discussion of septin-9 (<i>SEPT9</i>) DNA hypermethylation for detecting colorectal cancer, which is by far the most developed epigenetic biomarker assay.
With the exception of SEPT9 which is currently being implemented as a screening test for CRC all other markers lacked reproducibility and standardization and were studied in relatively small population samples.
This study aims to investigate the significance of the clinicopathological factors on methylated SEPT9 performance in a symptomatic endoscopy cohort, with a specific focus on colorectal cancer.
Herein, we tested whether combined use of APC, IGF2, MGMT, RASSF1A, and SEPT9 promoter methylation might accurately detect CRC irrespective of molecular subtype.
The test comprises a qualitative assay for the polymerase chain reaction (PCR) detection of methylated Septin9 DNA, the presence of which is associated with colorectal cancer: however, positive results should be verified by colonoscopy or sigmoidoscopy.
This study aims to examine the influence of algorithm and subject-related factors, including cancer stage, age, sex, and cancer location, on the performance of the SEPT9 gene methylation test, an assay approved by the US FDA for colorectal cancer (CRC) screening.
ROC curves show that the areas under the curves of ADD2 and AKR1B1 are higher than that of SEPT9, which has been clinically used as a screening biomarker of CRC.
The USPSTF reviewed the evidence on the effectiveness of screening with colonoscopy, flexible sigmoidoscopy, computed tomography colonography, the guaiac-based fecal occult blood test, the fecal immunochemical test, the multitargeted stool DNA test, and the methylated SEPT9 DNA test in reducing the incidence of and mortality from colorectal cancer or all-cause mortality; the harms of these screening tests; and the test performance characteristics of these tests for detecting adenomatous polyps, advanced adenomas based on size, or both, as well as colorectal cancer.
These findings show that hypermethylation markers in blood are highly sensitive and specific for CRC detection, with methylated SEPT9 being particularly robust.