A first evaluation of the Septin 9 test in the Czech Republic


Authors: P. Sychra 1;  V. Procházka 1;  L. Roubalová 2;  J. Zapletalová 3;  M. Konečný 1
Authors‘ workplace: II. interní klinika –  gatroenterologická a hepatologická LF UP a FN Olomouc 1;  Oddělení klinické biochemie, FN Olomouc 2;  Ústav lékařské bio­fyziky, LF UP Olomouc 3
Published in: Gastroent Hepatol 2016; 70(4): 300-304
Category: Clinical and Experimental Gastroenterology: Original Article
doi: 10.14735/amgh2016300

Overview

Colorectal cancer still persists despite advances in diagnosis and therapy. The unfulfilled expectations of screening programs has led to the development of new tests based on molecular biology for early diagnosis. Reports over the past 15 years concerning the possibility of using epigenetic markers of colon cancer for colon cancer diagnosis led us to study the feasibility of using the Septin 9 test comprised in the Epi proColon Plasma Quick Kit on a group of 108 patients undergoing colonoscopy, the reference method. We were interested in the sensitivity and specificity of the test under our clinical conditions. Among the 108 patients, colonoscopy detected adenomas in 41, carcinomas in 21, and no findings in 46 persons. In the patients with negative colonoscopic findings, the Septin 9 test was negative for 34 and positive for two, with 10 people were classified as “not detected” (ND) because the DNA concentration in the isobath was below the required level. In patients with a confirmed adenoma, the Septin 9 test was negative in 26 and positive in one, and 14 people were classified as ND. In patients with cancer, the Septin 9 test was negative in seven and positive in seven, and seven were classified as ND. The sensitivity of the Septin 9 assay was 19.5% and the specificity was 94.4%. Septin 9 test positivity was found significantly more often in people with cancer than in those with an adenoma or with negative findings on colonoscopy (p = 0.003). The Septin 9 test showed a high degree of specificity (94.4%). It was disappointing that the test showed very low sensitivity in patients with adenoma (only 3.7%). The overall results of the study were affected by the high proportion of tests in which the concentration of DNA in the isolate was insufficient, necessitating that these patients be classified as ND.

Key words:
septins – Septin 9 – sensitivity – specificity – colorectal neoplasms

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.

Submitted:
7. 7. 2016

Accepted:
8. 8. 2016


Sources

1. Kocna P, Vanickova Z, Zima T. Laboratory screen­ing markers in gastroenerology –  state of the art. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2013; 157(2): 91– 97. doi: 10.5507/ bp.2013.027.

2. Fric P, Zavoral M, Dvorakova H et al. An adapted program of colorectal cancer screening – 7 years experience and cost-benefit analysis. Hepato-gastroenterology 1994; 41(5): 413– 416.

3. Zavoral M, Suchanek S, Majek O et al. Colorectal cancer screening: 20 years of development and recent progres­s. World J Gastroenterol 2014; 20(14): 3825– 3834. doi: 10.3748/ wjg.v20.i14.3825.

4. Suchanek S, Majek O, Vojtechova G et al. Colorectal cancer prevention in the Czech Republic: time trends in performance indicators and cur­rent situation after 10 years of screen­ing. Eur J Cancer Prev 2014; 23(1): 18– 26. doi: 10.1097/ CEJ.0b013e328364f203.

5. Wohl P, Bednařík M, Wohl P et al. Comparison of various strategies for colorectal cancer screen­ing tests. Eur J Gastroenterol Hepatol 2011; 23(12): 1157– 1164. doi: 10.1097/ MEG.0b013e3283491438.

6. Fukushige S, Horii A. DNA methylation in cancer: a gene silenc­ing mechanism and the clinical potential of its bio­markers. Tohoku J Exp Med 2013; 229(3): 173– 185.

7. Grützmann R, Molnar B, Pilarsky C et al. Sensitive detection of colorectal cancer in peripheral blood by Septin 9 DNA methy­lation as­say. PLoS One 2008; 3(11): e3759. doi: 10.1371/ journal.pone.0003759.

8. War­ren JD, Xiong W, Bunker AM. Septin 9 methylated DNA is a sensitive and specific blood test for colorectal cancer. BMC Med 2011; 9: 133. doi: 10.1186/ 1741-7015-9-133.

9. Ahlquist DA, Taylor WR, Mahoney DW et al. The stool DNA test is more accurate than the plasma Septin 9 test in detect­ing colorectal neoplasia. Clin Gastroenterol Hepatol 2012; 10(3): 272– 277. doi: 10.1016/ j.cgh.2011.10.008.

10. Tóth K, Sipos F, Kalmár A et al. Detection of methylated SEPT9 in plasma is a reliable screen­ing method for both left- and right-sided colon cancers. PLoS One 2012; 7(9): e46000. doi: 10.1371/ journal.pone.0046000.

11. Ladabaum U, Al­len J, Wandell M et al. Colorectal cancer screen­ing with blood-based bio­markers: cost-ef­fectiveness of methy­lated Septin 9 DNA versus cur­rent strategies. Cancer Epidemiol Biomarkers Prev 2013; 22(9): 1567– 1576. doi: 10.1158/ 1055-9965.EPI-13-0204.

12. Ladabaum U, Alvarez-Osorio L, Rosch T et al. Cost-ef­fectiveness of colorectal cancer screen­ing in Germany: cur­rent endoscopic and fecal test­ing strategies versus plasma methylated Septin 9 DNA. Endosc Int Open 2013; 2(2): E96– E104. doi: 10.1055/ s-0034-1377182.

13. Johnson DA, Barclay RL, Mergener K et al. Plasma Septin9 versus fecal im­munochemical test­ing for colorectal cancer screening: a prospective multicenter study. PLos One 2014; 9(6): e98238. doi: 10.1371/ journal.pone.0098238.

14. Church TR, Wandell M, Lofton-Day C et al. Prospective evaluation of methylated SEPT9 in plasma for detection of asymp­tomatic colorectal cancer. Gut 2014; 63(2): 317– 325. doi: 10.1136/ gutjnl-2012-304149.

15. Molnár B, Tóth K, Barták BK et al. Plasma methylated septin 9: a colorectal cancer screen­ing marker. Expert Rev Mol Dia­gn 2015; 15(2): 171– 184. doi: 10.1586/  14737159.2015.975212.

16. Jin P, Kang Q, Wang X et al. Performance of a second-generation methyl­ated SEPT9 test in detect­ing colorectal neoplasm. J Gastroenterol Hepatol 2015; 30(5): 830– 833. doi: 10.1111/ jgh.12855.

17. Li B, Gan A, Chen X et al. Performance of DNA hypermethylation markers in peripheral blood for the detection of colorectal cancer: a meta-analysis and systematic review. PLoS One 2016; 11(5): e0155095. doi: 10.1371/ journal.pone.0155095.

Labels
Paediatric gastroenterology Gastroenterology and hepatology Surgery

Article was published in

Gastroenterology and Hepatology

Issue 4

2016 Issue 4

Most read in this issue

This topic is also in:


Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account