Evaluation of a Three-Marker Panel for the Detection of Uveal Melanoma Metastases: A Single-Center Retrospective Analysis.

Zenan Lin,Daniela Süsskind

doi:10.3390/cancers13102464

Abstract

Simple SummaryBlood-based B-cell activating factor (BAFF), growth differentiation factor-15 (GDF-15) and osteopontin (OPN) have been reported to be biomarkers for the uveal melanoma (UM) metastases. This work intended to assess their kinetics and to evaluate their significance as a three-marker panel for clinical practice. Our results not only provided their cutoff values for differentiating the metastatic patients from non-metastatic patients, but also confirmed that the three-marker panel outperformed any single biomarker in distinguishing metastatic patients. Besides, the increasing trends of the levels of three biomarkers were detected in the two-year period before the imaging diagnosis of metastases. The multiplex panel of BAFF, GDF-15 and OPN might be a utilizable implementation for the detection of UM metastases. Since it is a retrospective pilot work, more well-designed prospective studies employing larger cohorts are still needed to validate the findings.Blood-based B-cell activating factor (BAFF), growth differentiation factor-15 (GDF-15) and osteopontin (OPN) have been identified to be promising biomarkers for the metastases of uveal melanoma (UM). This study intended to assess their kinetics and to evaluate their significance as a three-marker panel. A group of 36 UM patients with and 137 patients without metastases were included in the study. Their plasma OPN levels were measured by ELISA; serum BAFF and GDF-15 levels were determined with a Luminex MAGPIX system. Receiver operating characteristic (ROC) analysis was performed to calculate the cutoff values of the three markers for identifying the patients with metastases. The ability to identify patients with metastases was compared between the single markers and the combination as a three-marker panel. By using the Student’s t-test, we also investigated the kinetic changes of the levels of BAFF, GDF-15 and OPN across six periods (i.e., 0–6 months, 6–12 months, 12–18 months, 18–24 months, >24 months and post-metastasis) before the imaging diagnosis of metastases. By maximizing the Youden’s index, the serum GDF-15 level of 1209 pg/mL and the plasma OPN level of 92 ng/mL were identified to have the best performance for distinguishing the metastatic patients from non-metastatic patients. The three-marker panel offered a better performance in distinguishing patients with metastases, with an area under the curve of 0.802, than any single biomarker. Increasing trends of the levels of three biomarkers were observed in the two-year period before the imaging diagnosis of metastases. The combined panel of BAFF, GDF-15 and OPN might be a utilizable implementation for the detection of UM metastases. In the bioinformatics study with two external datasets, the high expression of gene BAFF and GDF-15 in primary UM tissues was identified to be associated with poor overall survival rates. As the current work is a single-center retrospective study, more well-designed prospective investigations employing larger cohorts are urgently needed to validate our findings.

Highlights

As the most common primary intraocular malignancy, uveal melanoma (UM) was reported to have an incidence of six per one million in America and Europe [1]
We found that the ln(serum BAFF) levels were significantly higher in metastatic patients than in those without metastases and healthy controls [9]
The results suggested that the patients with metastases had significantly higher levels of ln(serum GDF−15) than those without metastases

Summary

Introduction

As the most common primary intraocular malignancy, uveal melanoma (UM) was reported to have an incidence of six per one million in America and Europe [1]. Various forms of therapeutic eye preserving approaches such as radiotherapy and local resection are available to treat the primary UM. Despite the surgical interventions for resectable metastatic lesions, few conventional therapeutic methods were found to be effective in treating the metastatic UM [1]. Novel treatments such as chemotherapies and immune checkpoint inhibitors, which were effective for metastatic cutaneous melanoma, demonstrated poor outcomes for metastatic UM [1,2]. An early diagnosis of the metastases is assumed to allow an on-time surgical resection and provide better chances of curing

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