Clinical significance of large tenascin-C spliced variant as a potential biomarker for colorectal cancer.

BACKGROUND: Tenascin-C is an extracellular matrix protein forming various types of spliced variants. Low molecule variants are transiently present, but large spliced variants are predominantly overexpressed in proliferative processes or tumorigenesis in some varieties of cancer. However, the detection of the plasma level of large tenascin-C spliced variant (L-Tn-CSV) in colorectal cancer (CRC) has not been clarified. This study was performed to validate elevated plasma L-Tn-CSV levels as a possible biomarker for CRC. MATERIALS AND METHODS: Plasma samples were obtained before resection and from time to time postoperatively and stored at -80 degrees C until assay. Plasma L-Tn-CSV levels were evaluated in patients with primary (n = 162) and with recurrent (n = 20) CRC, including 48 healthy volunteers, measured by ELISA. RESULTS: The average plasma L-Tn-CSV concentrations of patients with primary CRC were 5,260 +/- 3,243.3 pg/ml and of patients with recurrent CRC 4,106 +/- 2,261.1 pg/ml, which were significantly elevated in comparison with those of healthy volunteers (2,364.3 +/- 7,49.6). The sensitivity for detecting CRC using plasma L-Tn-CSV was 56.6%, based on the mean +/- 2 SD of the concentrations of healthy controls (3,863.5), which was significantly higher than CEA (40.1%) and CA19-9 (23.6%). No obvious associations were evident between plasma L-Tn-CSV status and values of CEA and CA19-9 respectively. Statistically significant differences in plasma L-Tn-CSV were observed depending on tumor depth, lymph node metastasis, and TNM stage. Negative conversions of plasma L-Tn-CSV levels 6 months after resection were significantly higher in the completely curative resection group than in the non-curative groups (P < 0.001). CONCLUSION: The plasma L-Tn-CSV may serve very well as a useful biomarker for tumor staging and postoperative monitoring of preoperatively positive CRC that is independent and exceeds conventional tumor markers.