Prognostic Implications of Tenascin C in Peripheral Blood and Primary Tumors at the Time of Uveal Melanoma Diagnosis

Abstract

To examine the prognostic implication of tenascin C (TNC) in posterior uveal melanoma (UM). Retrospective cohort study. A total of 162 patients diagnosed with posterior UM. A peripheral blood sample was obtained from 82 patients at the time of UM diagnosis between 1996 and 1999. Samples were kept frozen at -80°C until the concentration of TNC was measured in 2021. Primary tumour TNC RNA sequencing data were collected from another 80 patients (The Cancer Genome Atlas cohort). Patients were separated based on median TNC values. Cumulative incidences of metastatic death (UM mortality) from competing risks data were calculated as well as Cox regression hazard ratios. Patients with high and low TNC levels had tumours of similar size and American Joint Committee on Cancer stage at Bonferroni-corrected significance levels. The exception was a significantly smaller tumour diameter in patients with high serum TNC levels (p = 0.003). In competing risks analysis, patients with high serum TNC levels (≥7 ng/mL) had a higher UM mortality rate (44% vs 17% at 20 years; p = 0.008). Similarly, patients with higher primary tumour TNC RNA levels (≥1 transcripts per million) had higher UM mortality (83% vs 27% at 5 years; p = 0.003). In multivariate Cox regressions, TNC levels in peripheral blood and primary tumours were predictors of metastatic death independent of American Joint Committee on Cancer stage. TNC is a prognostic biomarker in UM. At the time of primary tumour diagnosis, it is measured in higher levels in both peripheral blood and tumour tissue from patients who will eventually suffer from metastatic death.