The Pathological Features of Colorectal Cancer Determine the Detection Performance on Blood ctDNA

Abstract

Background and Aim:Methylated SEPT9 is a novel circulating tumor DNA marker for colorectal cancer, while the effects of various colorectal cancer clinicopathological factors on its detection performance have not been fully evaluated. 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.Methods:A total of 1160 participants were recruited in this study, including 300 patients with colorectal cancer, 122 patients with adenoma, 103 patients with hyperplastic polyps, 568 normal participants (no evidence of disease), and 67 patients with other gastrointestinal diseases. Peripheral blood samples of these participants were collected from 3 Chinese hospitals, and the methylated SEPT9 level was measured using the Epi proColon 2.0 assay.Results:Cancer stage, size, and invasion depth were positively correlated with the detection sensitivity, while no difference in sensitivity was identified among cancers at various locations. Infiltrative colorectal cancer exhibited higher sensitivity than ulcerative and protrude colorectal cancer, while no difference in sensitivity was observed among assessed histological types. The colorectal cancer differentiation showed a clear correlation with the cancer stage, and moderate and poorly differentiated colorectal cancer exhibited higher sensitivity than well-differentiated colorectal cancer. Furthermore, colorectal cancer with distal metastasis (M1) showed higher sensitivity than those without any metastasis, while colorectal cancer with lymph node metastasis (N1 and N2) did not show statistical significance compared to those without it. Finally, local vessel or nerve invasion did not affect the sensitivity.Conclusion:Factors that reflect the colorectal cancer intrinsic properties, including cancer stage, size, invasion depth, classification, differentiation, and metastasis, exhibited significant effect on the mSEPT9 detection performance.

Age‐stratified reference intervals unlock the clinical potential of circulating cell‐free DNA as a biomarker of poor outcome for healthy individuals and patients with colorectal cancer

“…Tumor characteristics associated with high cfDNA levels also included large tumor size. It has previously been shown that increased circulating tumor DNA (ctDNA) levels were associated with a tumor size above 5 cm 43 . This corroborates the present findings, as ctDNA is part of the total cfDNA quantity.…”

“…Furthermore, comparable cfDNA levels in healthy individuals and Stages I to III CRC were found; only patients with disseminated disease (Stage IV) had significantly increased cfDNA levels. This finding was supported by other previous reports 9,43 . Tumor characteristics associated with high cfDNA levels also included large tumor size.…”

“…This finding was supported by other previous reports. 9,43 Tumor characteristics associated with high cfDNA levels also included large tumor size. It has previously been shown that increased circulating tumor DNA (ctDNA) levels were associated with a tumor size above 5 cm.…”

Improved diagnostic value by combining plasma PON1 level with tumor biomarkers in Colorectal Cancer patients

“…Blood-based test is a new option. For example, although SEPT9 DNA in plasma has become a marker for CRC 7 , 8 , its penetration still at a low rate due to its high price. Therefore, there is a need for methods with high sensitivity, high specificity and patient compliance.…”

Epigenetic IVD Tests for Personalized Precision Medicine in Cancer

“…The results obtained by Song et al (2018) and He et al (2018) suggest that the methylation status of SEPT9 could be applied to CRC stage, size, invasion depth, future risk assessment, metastasis, disease progression monitoring, and therapeutic effect evaluation. A possible flaw of this test is that Epi proColon ® detected the methylated status of the same region of the SEPT9 gene in some patients affected by other cancers (i.e., prostate, breast, lung or other diseases, hypertension, hyperlipidemia, diverticulitis, chronic gastritis, or cardiovascular) and according to their age (Ørntoft et al, 2015).…”