Detection of methylated septin 9 in tissue and plasma of colorectal patients with neoplasia and the relationship to the amount of circulating cell-free DNA
- PMID: 25526039
- PMCID: PMC4272286
- DOI: 10.1371/journal.pone.0115415
Detection of methylated septin 9 in tissue and plasma of colorectal patients with neoplasia and the relationship to the amount of circulating cell-free DNA
Abstract
Background: Determination of methylated Septin 9 (mSEPT9) in plasma has been shown to be a sensitive and specific biomarker for colorectal cancer (CRC). However, the relationship between methylated DNA in plasma and colon tissue of the same subjects has not been reported.
Methods: Plasma and matching biopsy samples were collected from 24 patients with no evidence of disease (NED), 26 patients with adenoma and 34 patients with CRC. Following bisulfite conversion of DNA a commercial RT-PCR assay was used to determine the total amount of DNA in each sample and the fraction of mSEPT9 DNA. The Septin-9 protein was assessed using immunohistochemistry.
Results: The percent of methylated reference (PMR) values for SEPT9 above a PMR threshold of 1% were detected in 4.2% (1/24) of NED, 100% (26/26) of adenoma and 97.1% (33/34) of CRC tissues. PMR differences between NED vs. adenoma and NED vs. CRC comparisons were significant (p<0.001). In matching plasma samples using a PMR cut-off level of 0.01%, SEPT9 methylation was 8.3% (2/24) of NED, 30.8% (8/26) of adenoma and 88.2% (30/34) of CRC. Significant PMR differences were observed between NED vs. CRC (p<0.01) and adenoma vs. CRC (p<0.01). Significant differences (p<0.01) were found in the amount of cfDNA (circulating cell-free DNA) between NED and CRC, and a modest correlation was observed between mSEPT9 concentration and cfDNA of cancer (R2 = 0.48). The level of Septin-9 protein in tissues was inversely correlated to mSEPT9 levels with abundant expression in normals, and diminished expression in adenomas and tumors.
Conclusions: Methylated SEPT9 was detected in all tissue samples. In plasma samples, elevated mSEPT9 values were detected in CRC, but not in adenomas. Tissue levels of mSEPT9 alone are not sufficient to predict mSEPT9 levels in plasma. Additional parameters including the amount of cfDNA in plasma appear to also play a role.
Conflict of interest statement
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4272286/bin/pone.0115415.g001.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4272286/bin/pone.0115415.g002.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4272286/bin/pone.0115415.g003.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4272286/bin/pone.0115415.g004.gif)
Similar articles
-
Clinical value of preoperative methylated septin 9 in Chinese colorectal cancer patients.World J Gastroenterol. 2019 May 7;25(17):2099-2109. doi: 10.3748/wjg.v25.i17.2099. World J Gastroenterol. 2019. PMID: 31114136 Free PMC article.
-
Circadian Rhythm of Methylated Septin 9, Cell-Free DNA Amount and Tumor Markers in Colorectal Cancer Patients.Pathol Oncol Res. 2017 Jul;23(3):699-706. doi: 10.1007/s12253-016-0174-2. Epub 2016 Dec 30. Pathol Oncol Res. 2017. PMID: 28035516
-
Detection of Methylated SEPT9 in Korean Colorectal Cancer Patients: Comparison with Previous Studies.Clin Lab. 2018 Sep 1;64(9):1573-1579. doi: 10.7754/Clin.Lab.2018.180551. Clin Lab. 2018. PMID: 30273999
-
A systematic review of the performance of the SEPT9 gene methylation assay in colorectal cancer screening, monitoring, diagnosis and prognosis.Cancer Biomark. 2017;18(4):425-432. doi: 10.3233/CBM-160321. Cancer Biomark. 2017. PMID: 28128742 Review.
-
Methylated Septin 9 as a Promising Biomarker in the Diagnosis and Recurrence Monitoring of Colorectal Cancer.Dis Markers. 2022 Jul 2;2022:7087885. doi: 10.1155/2022/7087885. eCollection 2022. Dis Markers. 2022. PMID: 35818587 Free PMC article. Review.
Cited by
-
DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine.Explor Target Antitumor Ther. 2024;5(1):34-53. doi: 10.37349/etat.2024.00203. Epub 2024 Jan 28. Explor Target Antitumor Ther. 2024. PMID: 38464391 Free PMC article. Review.
-
Complete Blood Count Alterations Prior to the Diagnosis of Colorectal Cancer May Help in the Detection of Synchronous Liver Metastases.J Clin Med. 2023 Oct 15;12(20):6540. doi: 10.3390/jcm12206540. J Clin Med. 2023. PMID: 37892677 Free PMC article.
-
Effects of obesity, and of weight loss following bariatric surgery, on methylation of DNA from the rectal mucosa and in cell-free DNA from blood.Int J Obes (Lond). 2023 Dec;47(12):1278-1285. doi: 10.1038/s41366-023-01384-4. Epub 2023 Sep 15. Int J Obes (Lond). 2023. PMID: 37714902
-
Health Economic Evidence and Modeling Challenges for Liquid Biopsy Assays in Cancer Management: A Systematic Literature Review.Pharmacoeconomics. 2023 Oct;41(10):1229-1248. doi: 10.1007/s40273-023-01292-5. Epub 2023 Jun 23. Pharmacoeconomics. 2023. PMID: 37351802 Free PMC article.
-
The Clinical Significance of Septin 9 and Colon Cancer Specific Antigen-2 (CCSA-2) in Colorectal Cancer.Asian Pac J Cancer Prev. 2023 Mar 1;24(3):1027-1036. doi: 10.31557/APJCP.2023.24.3.1027. Asian Pac J Cancer Prev. 2023. PMID: 36974558 Free PMC article.
References
-
- Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, et al. (2007) Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 18:581–592. - PubMed
-
- Pignone M, Saha S, Hoerger T, Mandelblatt J (2002) Cost-effectiveness analyses of colorectal cancer screening: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 137:96–104. - PubMed
-
- Siegel R, Desantis C, Virgo K, Stein K, Mariotto A, et al. (2012) Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin 62:220–241. - PubMed
-
- Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, et al. (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532. - PubMed
-
- Smith RA, Cokkinides V, Brooks D, Saslow D, Brawley OW (2010) Cancer screening in the United States, 2010: a review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin 60:99–119. - PubMed
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical