Serum coiled‑coil domain containing 25 protein as a potential screening/diagnostic biomarker for cholangiocarcinoma

Abstract

Coiled-coil domain containing 25 (CCDC25) was previously reported to be upregulated in cholangiocarcinoma (CCA) tissues compared with adjacent normal tissues. The present study investigated whether serum CCDC25 level may be used as a potential marker for the diagnosis of CCA. Bioinformatics tools were used to reveal that CCDC25 is secreted into plasma/serum via a non-conventional pathway, which secretes proteins independently from the endoplasmic reticulum/golgi complex, but is yet to be fully elucidated. Subsequently, the CCDC25 levels in the sera of patients with CCA (n=141), patients with benign biliary disease (BBD; n=53) and healthy controls (HC; n=72) were measured using a quantitative dot blot assay based on the standard curve created using recombinant CCDC25 protein. The results demonstrated that the serum CCDC25 level in the CCA group (0.28±0.06 ng/µl) was significantly higher compared with that in the BBD (0.15±0.03 ng/µl) or HC (0.0017±0.0008 ng/µl) groups. Serum CCDC25 level provided an improved resolution (P=0.0001) compared with carcinoembryonic antigen (P=0.098) or carbohydrate antigen 19-9 (P=0.271) for the differential diagnosis between BBD and CCA. Receiver operating characteristic curve analysis revealed high sensitivity and specificity of serum CCDC25 level to differentiate between patients with CCA and HC (93.0 and 100%, respectively), and also to differentiate between patients with CCA and patients with BBD (75.0 and 84.0%, respectively). CCDC25 expression was further investigated in 23 CCA tissues, and CCDC25 expression in cancer tissues was moderately correlated with the serum CCDC25 level (r 2 =0.52, P=0.01). Among patients with CCA, serum CCDC25 level was significantly higher in patients with non-metastatic CCA compared with patients with metastatic CCA. Correspondingly, a higher serum CCDC25 level was associated with a longer overall survival time in patients with CCA. In conclusion, serum CCDC25 level may be a promising screening and diagnostic marker for the differential diagnosis of CCA.

Proteomics-Based Identification of Salivary Changes in Patients with Burning Mouth Syndrome

“…To the best of our knowledge, coiled-coil domain-containing protein 25 (CCDC25) has been described in relation to BMS in this study for the first time. This protein is highly conserved among mammals and its expression is almost ubiquitous in human tissues; however, its function is still unclear [ 31 ]. This protein has been proposed recently as a serum biomarker of chronic cholangitis and cholangiocarcinoma [ 31 ].…”

“…This protein is highly conserved among mammals and its expression is almost ubiquitous in human tissues; however, its function is still unclear [ 31 ]. This protein has been proposed recently as a serum biomarker of chronic cholangitis and cholangiocarcinoma [ 31 ]. However, there is no data about CCDC25 and saliva or BMS and, therefore, further studies should be performed to clarify its possible relation.…”

High Level of Serum Coiled-coil Domain Containing 25 (CCDC25) as a Diagnostic Marker for Cholangiocarcinoma But Not for Other Cancers

“…In our previous study (6), we reported that CCDC25 was intracellularly overexpressed in CCA cells, especially after bile acid treatment, and was overexpressed in CCA tissues in comparison to the corresponding adjacent noncancerous tissues. We also reported that the serum CCDC25 level of CCA patients was higher than that of healthy controls, suggesting that CCDC25 can be a diagnostic biomarker for CCA (7). In this study, therefore, we examined CCDC25 levels in the patients' sera from highly prevalence cancers in Thailand including CRC, BC, HCC, and CCA, to evaluate their diagnostic value.…”

Serum Angiopoietin-Like Protein 4: A Potential Prognostic Biomarker for Prediction of Vascular Invasion and Lymph Node Metastasis in Cholangiocarcinoma Patients

“…For instance, apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX-1) was a secreted protein which identified as a potential serum marker for diagnosis and prognosis of CCA ( 16 ). Moreover, other members of our group identified coiled-coil domain containing 25 (CCDC25), apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) and cytokine-induced apoptosis inhibitor 1 (CIAPIN1) as potential secreted protein biomarkers in CCA ( 17 – 19 ). In this study, we performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of CCA patients' sera who were pathologically diagnosed with both vascular invasion and lymph node metastasis with ≤ 1 year survival time and >1 year survival time for searching a potential prognostic biomarker of CCA.…”