Performance Comparison Between Plasma and Stool Methylated SEPT9 Tests for Detecting Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the most common type of malignancies of the gastrointestinal tract worldwide. Plasma methylated SEPT9 test has been used clinically for CRC screening for several years, but the study about the performance comparison between plasma and stool has rarely been reported. In this study, 124 plasma samples, 100 stool samples, and 60 sets of plasma and paired stool samples were collected and tested by a methylated SEPT9 test in three PCR replicates. The results indicated methylated SEPT9 levels in stool samples were significant higher than those in plasma samples (p < 0.0001). When a plasma sample was called positive if 1 out of 3 PCR replicates was positive and a stool sample was called positive if 3 out of 3 PCR replicates were positive with a mean Cp value of less than 40.0, stool methylated SEPT9 test achieved similar sensitivity (83.3% vs 85.6%) and specificity (92.1% vs 90.1%) to those by plasma methylated SEPT9 test, and the overall concordance rate is 78.3%. However, stool methylated SEPT9 test showed 35.9 and 7.9% improvement in detecting advanced adenomas (AA) and stage I-II CRC in comparison to plasma methylated SEPT9 test. The AUC for plasma methylated SEPT9 and stool methylated SEPT9 in detecting CRC were 0.885 (95% CI: 0.832-0.938) and 0.935 (95% CI: 0.895-0.975), respectively. In conclusion, stool methylated SEPT9 test showed higher sensitivities for detection AA and early stage CRC compared with plasma methylated SEPT9 test, and stool methylated SEPT9 test may be a more suitable tool for early stage CRC screening.

KCNQ5 and C9orf50 Methylation in Stool DNA for Early Detection of Colorectal Cancer

“…Therefore, it is conceivable that tumor DNA was more concentrated in stool than in plasma, resulting in a higher sensitivity for CRC detection with stool samples. Such a phenomenon was also observed for methylated SEPT9 and methylated SDC2 in our previous studies (50,56,57). When compared to other methylation biomarkers in stoolbased tests, the sensitivities of methylated C9orf50 and methylated KCNQ5 for all stage CRC detection, 85.9 and 77.3% respectively, fell within the range of other markers from 71.2% for methylated HPP1 (55) to 92.5% for methylated COL4A2 (33).…”

Feasibility of Methylated CLIP4 in Stool for Early Detection of Colorectal Cancer: A Training Study in Chinese Population

“…A direct comparison study found significantly higher m SEPT9 level in stool samples than in plasma. Whereas the performance of both tests in detecting all stage CRC was similar, stool m SEPT9 test achieved improvement of 35.9% and 7.9% in sensitivity for detecting AA and stage I-II CRC when compared to plasma test ( 31 ). Jensen et al identified three methylation markers, C9orf50 , KCNQ5 , and CLIP4 , and evaluated their performance for CRC detection with plasma samples.…”

Promising Epigenetic Biomarkers for the Early Detection of Colorectal Cancer: A Systematic Review

“…We examined the last five years’ literature for methylated genes currently targeted by FDA or NMPA screening kits: mSDC2, mSEPT9, mNDRG4, and mBMP3. With our specific filters, we found six studies dedicated to mSDC2 [ 33 , 34 , 35 , 36 , 37 , 38 ] and seven studies for mSEPT9 [ 39 , 40 , 41 , 42 , 43 , 44 , 45 ]; two described mBMP3 performance [ 46 , 47 ], while no study evaluated mNDRG4 alone. A multi-target approach evaluating these biomarkers and others was employed in 16 studies, 5 of them deciphering mSDC2 and mSEPT9 performance [ 48 , 49 , 50 , 51 , 52 ].…”

“…CpG island hypermethylation of the SEPT9 promoter leads to altered expression—eliminating its tumor suppressor activity, which contributes to carcinogenesis [ 54 ]. mSEPT9 was evaluated in four studies as a single biomarker [ 39 , 40 , 42 , 45 ]. Three studies compared mSEPT9 performance with other known screening tools [ 41 , 43 , 44 ] ( Table S2 ).…”