Cell Secretome Analysis Using Hollow Fiber Culture System Leads to the Discovery of CLIC1 Protein as a Novel Plasma Marker for Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southeast Asia. Unfortunately, most NPC victims have had metastasis when first diagnosed due to its deep location and vague symptoms. To date, discovery of sensitive and specific biomarkers for improving detection of NPC remains a challenge. Our previous study established a strategy for cell secretome analysis using a hollow fiber culture (HFC) system combined with liquid chromatography mass spectrometry. Herein, the above platform was used to collect NPC secretome for the discovery of relevant clinical biomarkers. Among 66 identified proteins, chloride intracellular channel 1 (CLIC1) was sieved out for intended use as a potential NPC biomarker candidate. Approximately 75% of NPC tissue specimens showed positive CLIC1 staining by IHC. The plasma levels of CLIC1 in NPC patients (N = 70), as presented by sandwich ELISA, were significantly higher than those in the healthy controls (N = 74) (mean +/- SD, 16.38 +/- 26.53 vs 2.39 +/- 5.32 mu/mL; p = 0.00005). Using a cutoff point of 2.58 mu g/mL, CLIC1 successfully discriminated NPC from the benign healthy control group with a sensitivity of 63% and a specificity of 77%. The area under the receiver operating characteristic curve was determined to be 0.74 (95% Cl, 0.652-0.818). The statistical analysis of CLIC1 level in plasma shows that CLIC1 could be applied as a marker for early detection of NPC. This is the first report for the detection of CLIC1 as a plasma marker. Our results indicate that the analytical platform could provide a feasible strategy to profile tumor cell secretome for identifying cancer biomarkers, and CLIC1 may be a novel plasma tumor marker for NPC.