A First Step to a Biomarker of Curative Surgery in Colorectal Cancer by Liquid Biopsy of Methylated Septin 9 Gene

Abstract

Objectives. To confirm that patients affected by colorectal cancer have the V2 region of Septin 9 (SEPT9) gene hypermethylated in the circulating free DNA from a peripheral blood sample before surgery and to determine if this hypermethylated DNA disappears from the patients after complete resection of the tumour. Methods. Plasma from 10 patients with colorectal cancer was collected preoperative and three months after surgery. The analysis of the methylation status of the promoter region of the SEPT9 gene was performed using a 7500 Fast Real-Time PCR System. Results. Hypermethylation of SEPT9 gene was detected in 8 out of 10 preoperative samples (one negative result was probed to be a Lynch syndrome) and in 4 out of 10 postoperative samples matching with the cases of recurrence or persistence of disease. This means that, in this sample, the preoperative sensitivity and specificity of the test were 88.9% and 100%, respectively, and there is 100% correlation between the positive results of the SEPT9 test and a recurrence/persistence of the disease in patients after surgical resection. Conclusions. Our study shows that circulating hypermethylated SEPT9 is a specific colorectal cancer biomarker. This hypermethylated SEPT9 DNA disappears around three months after surgery and that circulating hypermethylated SEPT9 may be the first noninvasive marker for postsurgical diagnosis; this conclusion must be confirmed with a more significant number of patients.

Extracellular Nucleic Acids in the Diagnosis and Progression of Colorectal Cancer

“…Hypermethylated SEPT9 ctDNA disappears after 3 months following surgery, suggesting that this molecule may be the first non-invasive biomarker for postsurgical follow-up [ 82 , 83 ]. The plasma-based SEPT9 gene methylation assay is currently an FDA-approved non-invasive CRC screening test known as Epi proColon ® 1.0 [ 79 , 84 ].…”

Clinical Applications of Minimal Residual Disease Assessments by Tumor-Informed and Tumor-Uninformed Circulating Tumor DNA in Colorectal Cancer

“…The COLVERA ® (Clinical Genomics, Bridgewater, NJ, USA) assay is a 2-gene ( BCAT1 / IKZF1 ) methylation-specific, plasma ctDNA platform that is also commercially available and has shown greater sensitivity for recurrence in resected, localized CRC than CEA [ 28 , 40 , 41 , 42 , 43 ]. Among the earlier genes whose methylation in ctDNA has been described in CRC includes SEPT9 , for which several groups have shown that postoperative ctDNA-positivity for SEPT9 carries high specificity for predicting recurrent CRC [ 44 , 45 , 46 , 47 , 48 ] while conferring a median lead time of 8 months prior to radiographic detection of recurrence in resected CRC patients [ 27 ].…”

Methylated Septin 9 as a Promising Biomarker in the Diagnosis and Recurrence Monitoring of Colorectal Cancer

“…Studies have shown that the rate of SEPT9 methylation in peripheral blood of patients with CRC is related to clinicopathological features; for example, SEPT9 methylation is positively correlated with the malignancy of CRC [11][12][13]. After radical resection of colorectal cancer, the level of mSEPT9 in peripheral blood decreases; however, the level increases after recurrence, suggesting that mSEPT9 in peripheral blood can be used for evaluating the pathological stages of CRC and may represent a molecular biological indicator for evaluating prognosis, recurrence, and metastasis [14,15]. However, the reported sensitivity and specificity values of plasma mSEPT9 are highly variable across studies, with the sensitivity ranging from 50.9-93.1% and specificity ranging from 62.2-93.8% [16,17].…”