Original Article
OSMR and SEPT9: promising biomarkers for detection of colorectal cancer based on blood-based tests
Abstract
Background: Early screening and monitoring of the stage of colorectal cancer (CRC) is crucial for successful treatment and patient survival. Our purpose was to identify that evaluating methylated oncostatin M receptor (mOSMR) and Septin 9 (mSEPT9) in plasma DNA could be a feasible method for CRC diagnosis.
Methods: Plasma samples (40 samples have matched cancer and adjacent non-cancer tissues) were collected from 187 patients with CRC, 25 patients with polyps and 109 healthy controls. qRT-PCR assay was used to analyze SEPT9 and OSMR mRNA levels. DNA bisulfite treatment, the levels of mSEPT9 and mOSMR in CRC tissues and plasma samples were evaluated by using fluorescence-based real-time PCR assay (MethyLight). mSEPT9 and mOSMR levels in plasma were compared before and after curative resection. Serum CEA, CA19-9, CA72-4 and CA242 were also measured and analyzed in parallel.
Results: SEPT9 and OSMR mRNA levels were significantly lower in CRC tissues compared with those in their adjacent noncancerous tissues (P=0.006 and 0.002, respectively). mSEPT9 and mOSMR were significantly higher in CRC tissues compared with those in their adjacent non-cancerous tissues (P<0.0001). Plasma mSEPT9 (cut-off value: 0.777) and mOSMR (0.796) had a sensitivity of 62.6% and 74.9% for CRC, and a specificity of 91.7% and 86.2%, respectively. mSEPT9 and mOSMR were positive in 12.0% and 20.0% in polyps, respectively. Moreover, combined mSEPT9 and mOSMR (77.0%) showed a higher sensitivity than CEA (32.9%), CA72.4 (20.4%), CA199 (13.9%) and CA242 (23.9%), and these blood biomarkers together had a higher sensitivity (83.0%) compared with these individual blood biomarkers.
Conclusions: OSMR methylation (mOSMR) in plasma is useful for diagnosis of CRC as a new biomarker, and the panel of tests to analyze mSEPT9, mOSMR, CEA, CA19-9, CA72-4 and CA242 appears to be feasible and convenient for the diagnosis of CRC.
Methods: Plasma samples (40 samples have matched cancer and adjacent non-cancer tissues) were collected from 187 patients with CRC, 25 patients with polyps and 109 healthy controls. qRT-PCR assay was used to analyze SEPT9 and OSMR mRNA levels. DNA bisulfite treatment, the levels of mSEPT9 and mOSMR in CRC tissues and plasma samples were evaluated by using fluorescence-based real-time PCR assay (MethyLight). mSEPT9 and mOSMR levels in plasma were compared before and after curative resection. Serum CEA, CA19-9, CA72-4 and CA242 were also measured and analyzed in parallel.
Results: SEPT9 and OSMR mRNA levels were significantly lower in CRC tissues compared with those in their adjacent noncancerous tissues (P=0.006 and 0.002, respectively). mSEPT9 and mOSMR were significantly higher in CRC tissues compared with those in their adjacent non-cancerous tissues (P<0.0001). Plasma mSEPT9 (cut-off value: 0.777) and mOSMR (0.796) had a sensitivity of 62.6% and 74.9% for CRC, and a specificity of 91.7% and 86.2%, respectively. mSEPT9 and mOSMR were positive in 12.0% and 20.0% in polyps, respectively. Moreover, combined mSEPT9 and mOSMR (77.0%) showed a higher sensitivity than CEA (32.9%), CA72.4 (20.4%), CA199 (13.9%) and CA242 (23.9%), and these blood biomarkers together had a higher sensitivity (83.0%) compared with these individual blood biomarkers.
Conclusions: OSMR methylation (mOSMR) in plasma is useful for diagnosis of CRC as a new biomarker, and the panel of tests to analyze mSEPT9, mOSMR, CEA, CA19-9, CA72-4 and CA242 appears to be feasible and convenient for the diagnosis of CRC.
