Performance of epigenetic markers SEPT9 and ALX4 in plasma for detection of colorectal precancerous lesions.
BACKGROUND
Screening for colorectal cancer (CRC) has shown to reduce cancer-related mortality, however, acceptance and compliance to current programmes are poor. Developing new, more acceptable non-invasive tests for the detection of cancerous and precancerous colorectal lesions would not only allow preselection of individuals for colonoscopy, but may also prevent cancer by removal of precancerous lesions.


METHODS
Plasma from 128 individuals (cohort I - exploratory study: 73 cases / 55 controls) was used to test the performance of a single marker, SEPT9, using a real-time quantitative PCR assay. To validate performance of SEPT9, plasma of 76 individuals (cohort II - validation study: 54 cases / 22 controls) was assessed. Additionally, improvement of predictive capability considering SEPT9 and additionally ALX4 methylation was investigated within these patients.


RESULTS
In both cohorts combined, methylation of SEPT9 was observed in 9% of controls (3/33), 29% of patients with colorectal precancerous lesions (27/94) and 73% of colorectal cancer patients (24/33). The presence of both SEPT9 and ALX4 markers was analysed in cohort II and was observed in 5% of controls (1/22) and 37% of patients with polyps (18/49). Interestingly, also 3/5 (60%) patients with colorectal cancer were tested positive by the two marker panel in plasma.


CONCLUSIONS
While these data confirm the detection rate of SEPT9 as a biomarker for colorectal cancer, they also show that methylated DNA from advanced precancerous colorectal lesions can be detected using a panel of two DNA methylation markers, ALX4 and SEPT9. If confirmed in larger studies these data indicate that screening for colorectal precancerous lesions with a blood-based test may be as feasible as screening for invasive cancer.
Tänzer
Marc
M
Department of Medicine II, Klinikum rechts der Isar, Technische Universität, München, Germany.
Balluff
Benjamin
B
Distler
Jürgen
J
Hale
Kari
K
Leodolter
Andreas
A
Röcken
Christoph
C
Molnar
Bela
B
Schmid
Roland
R
Lofton-Day
Catherine
C
Schuster
Tibor
T
Ebert
Matthias P A
MP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D012680:Sensitivity and Specificity; D058112:Septins; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
C416676:ALX4 protein, human; D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D019204:GTP-Binding Proteins; C474315:SEPTIN9 protein, human; D058112:Septins