Abstract
Since early diagnosis is very important for treating CRC, we decided to detect peripheral serum canopy fibroblast growth factor signaling regulator 2 (CNPY2) isoform 2 to verify its diagnostic value for CRC patients. Serum samples were collected from 430 CRC patients and 201 healthy controls. Enzyme-linked immunosorbent assay (ELISA) detection kits for CNPY2 isoform 2 were generated and then applied to measure serum CNPY2 isoform 2 concentrations. Serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were also measured. The median serum CNPY2 isoform 2 concentrations in all CRC patients were significantly higher than those in the healthy control group (all P<0.001). Those with stage I CRC presented the highest area under the receiver operating characteristic curve (AUC) for CNPY2 isoform 2 [0.707, 95% confidence interval (CI): 0.649-0.765, P<0.001]. The diagnostic efficiency of the combination of CNPY2 isoform 2, CEA and CA19-9 was significantly higher than that of each biomarker detected separately (all P<0.0167).Serum CNPY2 isoform 2 may be a valuable biomarker for the early detection of CRC and presents an improvement in the diagnostic efficiency by combination of CEA and CA19-9. Funding Statement: This study was funded by a grant from the Guangzhou Science and Technology Plan Projects (Health Medical Collaborative Innovation Program of Guangzhou) (grant No. 201400000001-4), the National Natural Science Foundation of China (NO. 81772595), Sun Yat-sen University ClinicalResearch 5010 Program (NO.2015024 and NO. 2013013). Declaration of Interests: The authors declare none. Ethics Approval Statement: This study was performed in accordance with the ethical standards of the World Medical Association Declaration of Helsinki. Study was approved by the Institutional Research Ethics Committee of Sun Yat-sen University Cancer Center (Approval number: B2017-042-01). The informed consents for using tissue samples, before the initial treatment, were obtained from the patients.
Highlights
Colorectal cancer (CRC), one of the most common newly diagnosed cancers, has been ranked as the third leading cause of cancer-related deaths in China and developed countries [1, 2]
The serum canopy fibroblast growth factor signaling regulator 2 (CNPY2) isoform 2 levels were significantly elevated in CRC patients at various stages compared with those in healthy controls, indicating that serum CNPY2 isoform 2 represents as a potential serum biomarker associated with CRC
Previous studies have shown that elevated levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were more sensitive for the diagnosis of advanced CRC, because elevated levels of these markers often indicate the occurrence of metastatic disease [18, 19]. These results revealed that the diagnostic values of serum CNPY2 isoform 2, CEA and CA19-9 might be complementary in all CRC patients
Summary
Colorectal cancer (CRC), one of the most common newly diagnosed cancers, has been ranked as the third leading cause of cancer-related deaths in China and developed countries [1, 2]. Metastatic CRC presents a poor 5year survival rate of less than 20% even when surgery and comprehensive treatment have been performed [3, 5]. Since peripheral blood can be non-invasively obtained and stored, detection of multiple serum biomarkers has become an alternative method for helping to make early diagnoses of CRC. Previous studies have reported that CEA and CA19-9 presented a diagnostic sensitivity of less than 50% [10, 11]. This means that more than half of CRC cases will be misdiagnosed on the basis of CEA or CA19-9 alone. The need to find more effective serum biomarkers for the early detection of CRC is urgent, as this would help optimize early CRC treatment
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