Quantitative assessment of the Septin9 biomarker for colorectal cancer recurrence monitoring

Purpose: DNA methylation biomarkers can be used to detect tumor-derived circulating DNA and diagnose colorectal cancer (CRC) in blood as demonstrated by the CE-marked Epi proColon for the detection of methylated-SEPT9 ( ^m SEPT9) in plasma. In addition to qualitative assessment of ^m SEPT9 for early detection, quantitative assessment of ^m SEPT9 could provide information to the physician following diagnosis.

Materials and methods: ^m SEPT9 and methylated-RASSF2A were measured using quantitative-PCR on bisulfite-converted DNA from CRC patient plasma taken before and following surgery. A multi-center clinical study was subsequently initiated with two goals: 1) determine whether either biomarker decreases after surgical resection using plasma from stages I-III patients taken prior to and following surgical resection; 2) determine whether either biomarker is elevated at the time of recurrence using plasma from curatively treated patients presenting with metachronous metastasis.

Results: 20/23 (87%) stage-II and 14/15 (93%) stage-III CRC patients were ^m SEPT9-positive, similar to previous reports. ^m SEPT9 in plasma was undetectable in 13/20 (65%) ^m SEPT9-positive stage-II CRC patients compared with 4/14 (28%) ^m SEPT9-positive stage-III patients following surgical resection. Methylated-RASSF2A showed similar performance. A multi-center clinical study has been initiated for verification in an independent sample set and to further explore biomarker kinetics following diagnosis.

Conclusion: Preliminary results indicated that detection of ^m SEPT9 and methylated-RASSF2A in CRC patient plasma following treatment with curative intent may provide prognostic information and may serve as an early indicator of disease recurrence.