CCSP-2 표적 나노바이오센서를 이용한 새로운 대장 종양 진단 혈액 검사
- Background A blood-based test for the early detection of colorectal cancer (CRC) would be an attractive alternative to current CRC screening tests. Colon cancer secreted protein-2 (CCSP-2) is a novel candidate blood marker for CRC, which was identified by gene expression microarray. The aims of this study were to assess the CCSP-2 expression patterns in a large number of human CRC tissues and to evaluate the possible clinical use of the CCSP-2 as a blood biomarker for the early diagnosis of CRC and adenomas.
Methods Immunohistochemical staining of CCSP-2 was performed in the colorectal tumor and paired normal tissue (10 advanced adenomas and 69 CRCs). The electric-field effect colorectal sensor (E-FECS), which is an ion-sensitive field-effect transistor under dual gate operation with nanostructure, was used to quantify CCSP-2 in human blood. Biosensor verification was performed on 10 controls and 10 CRC cases, and it was clinically validated on 30 controls, 30 advanced adenomas and 81 CRC cases.
Results CCSP-2 protein was homogenously expressed in all CRC and advanced adenoma tissues, whereas CCSP-2 was not detected in normal colorectal tissues. CCSP-2 levels in blood were significantly higher in the advanced adenoma and CRC patients compared with the controls (P = 0.005 and P = 0.001). There was no difference in the detection rate of CCSP-2 in blood between cancer stages (P = 0.067). The overall sensitivity of blood CCSP-2 in the diagnosis of colorectal tumors (including advanced adenomas and CRC) was 44.1%, and the specificity was 86.7% (AUC was 0.67, 95% confidence interval [CI] 0.57–0.76). The sensitivity and specificity for CRC were 44.4% and 86.7%, respectively, and the sensitivity and specificity for advanced adenomas were 43.3% and 86.7%, respectively.
Conclusions Our study showed that novel blood-based detection using a nanobiosensor targeting CCSP-2 could reveal about half of CRC and adenoma cases, irrespective of tumor stage. The utility of this method for CRC screening will require improved sensitivity, and further studies are needed to determine the role of this novel candidate blood marker in clinical practice.
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- CCSP-2; colorectal neoplasms; biomarkers; serum marker; field-effect biosensor
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