The new blood test biomarker SEPT9 and colorectal carcinoma screening

Czech version

Authors: Z. Beneš ¹; M. Šedivcová ²; Z. Antoš ¹; P. Kohout ¹; G. Puškárová ¹; M. Černík ¹; M. Rozmahel ¹; M. Shánělová ³; J. Dolina ³; A. Hep ³; M. Trubač ⁴; J. Stehlík ²; T. Vaněček ²; M. Michal ²; J. Šimša ⁴; Z. Kala ⁵
Authors‘ workplace: Interní oddělení Thomayerovy nemocnice Praha, přednosta doc. MU Dr. Zdeněk Beneš, CSc. ¹; Bioptická laboratoř s. r. o., Plzeň, vedoucí pracoviště prof. MU Dr. Alena Skálová, CSc. ²; Interní gastroenterologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MU Dr. Aleš Hep, CSc. ³; Chirurgická klinika Thomayerovy nemocnice a 1. lékařské fakulty UK Praha, přednosta doc. MU Dr. Jaromír Šimša, CSc. ⁴; Chirurgická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MU Dr. Zdeněk Kala, CSc. ⁵
Published in: Vnitř Lék 2013; 59(11): 971-976
Category: Original Contributions

Overview

Due to its high incidence and mortality rates, the colorectal carcinoma represents a crucial medical issue. However, when it is detected in early stage there is high rate of successful treatment. That’s why, early stage cancer screening programmes were introduced into the clinical practice. They focus on the finding of hidden bleeding, using various laboratory techniques, sigmoidoscopy, and, primarily, colonoscopy. However, screening programmes have not yet reached the effect required. New techniques are therefore being developed, such as the detection of blood biomarkers. This group includes also methylated SEPT9 (mSEPT9) detection in blood. We applied this test on 57 patients; we divided the group into two parts. There were 33 asymptomatic individuals in the first group. In this group, we were got only one positive mSEPT9 result. The consequent colonoscopies were negative. The other group had 24 proven carcinomas. Of them, two had negative mSEPT9 results. The remaining in all 22 patients was tested mSEPT9 positive. After its efficiency is tested by further studies, this test may be used especially for patients with low compliance, as it only requires routine blood drawing.

Key words:
colorectal carcinoma – screening programmes – SEPT9

Sources

1. Weiss G, Rösch T. Potential of new Blood Test for Colorectal Cancer S‑ The Septin 9 Gene Biomarker. Eur Oncol 2010; 6: 51– 54.

2. Dušek L, Mužík J, Hájek O et al. Kolorektální karcinom v ČR – data minulá a budoucí. Rozhl chir 2012; 91: 39– 43.

3. Schekenburger M, Dietrich M. Epigenetics Offer New Horizons for Colorectal Cancer Prevention. Curr Colorectal Cancer Rep 2012; 8: 66– 61.

4. Kim MS, Lee J, Sidarsky D. DNA methylation markers colorectal cancer. Cancer Metastasis Rev 2010; 29: 181– 206.

5. Grutzmann R, Molnar B, Pilarsky Ch et al. Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay. PLoS ONE 2008; 3: e3759.

6. Shapiro B, Chakrabarty M, Cohn EM et al. Determination of circulating DNA levels in patients with benign or malignit gastrointestinal disease. Cancer 1983; 51: 2116– 2120.

7. Kamat AA, Baldwin M, Urbauer D et al. Plasma cell‑free DNA in ovarian cancer: an independent prognostic biomarker. Cancer 2010; 116: 1918– 1925.

8. Gormally E, Hainaut P, Caboux E et al. Amount of DNA in plasma and cancer risk: a prospective study. Int J Cancer 2004; 111: 746– 749.

9. Diehl F, Li M, Dressman D et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci USA 2005; 102: 16368– 16373.

10. Herrera LJ, Raja S, Gooding WE et al. Quantitative analysis of circulating plasma DNA as a tumormarker in thoracic malignancies. Clin Chem 2005; 51: 113– 118.

11. Robertson KD. DNA methylation and chromatin: Unraveling the tangled web. Oncogene 2002; 21: 5361– 5379.

12. Szyf M. Targeting DNA methylation in cancer. Ageing Res Rev 2003; 2: 299– 328.

13. Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermetylation. N Engl J Med 2003; 349: 2042– 2054.

14. Ku JL, Jeon YK, Park JG. Methylation‑ specific PCR. Methods Mol Biol 2011; 791: 23– 32.

15. Nygren AO, Ameziane N, Duarte HM et al. Methylation‑ Specific MLPA (MS‑ MLPA): simultaneous detection of CpG methylation and copy number changes of up to 40 sequences. Nucleic Acids Res 2005; 33: e128.

16. Eads CA, Laird PW. Combined bisulfite restriction analysis (COBRA). Methods Mol Biol 2002; 200: 71– 85.

17. Li Y, Tollefsbol TO. DNA methylation detection: bisulfite genomic sequencing analysis. Methods Mol Biol 2011; 791: 11– 21.

18. Eads CA, Danenberg KD, Kawakami K et al. MethyLight: a high‑throughput assay to measure DNA methylation. Nucleic Acids Res 2000; 28: E32.

19. Zeschnigk M, Bohringer S, Price EA et al. A novel real‑ time PCR assay for quantitative analysis of methylated alleles (QAMA): analysis of the retinoblastoma locus. Nucleic Acids Res 2004; 32: E125.

20. Lofton‑ Day C, Model F, deVos T et al. DNA Metylation Biomarkers for Blood‑ Based Colorectal Cancer Screening. Clin Chem 2008; 54: 414– 423.

21. Li XQ, Guo YY, Wei D. DNA methylation and microRNAs in cancer. World J Gastroenterol 2012; 18: 882– 888.

22. deVos T, Tetzner R, Model F et al. Circulating Metylated SEPT9 DNA in Plasma Is a Biomarker for Colorectal Cancer. Clin Chem 2009; 55: 1337– 1346.

23. 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: e3759.

24. Warren JD, Xiong W, Bunker AM et al. Septin 9 methylated DNA is a sensitive and specific blood test for colorectal cancer. BMC Med 2011; 14: 133.

25. 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: e46000.

26. Lofton‑ Day C, Model F, De Vos T et al. DNA‑ -Methylation Biomarkers for‑ Based Colorectal Cancer Screening. Clin Chem 2008; 54: 1– 10.

27. Zavoral M, Frič P. Národní program screeningu sporadického kolorektálního karcinomu (KR‑ CA): Vývoj, současnost, perspektiva. Zdravotnické noviny, Lékařské listy 28.1.2013.

28. Tóth K, Galamb O, Spisák S et al. The influence of methylated septin 9 gene on RNA and protein level in colorectal cancer. Pathol Oncol Res 2011; 17: 503– 509.