4.6 Article

Exploring the role of BAFF as biomarker in the detection of uveal melanoma metastases

Journal

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Volume 147, Issue 5, Pages 1389-1405

Publisher

SPRINGER
DOI: 10.1007/s00432-021-03555-0

Keywords

B-cell activating factor; Uveal melanoma; Metastasis; Serum markers; Tumor microenvironment; Tumor-infiltrating immune cells

Categories

Funding

  1. China Scholarship Council (CSC) Program [201708080023]

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This study suggests that serum BAFF levels may serve as a potential marker for detecting UM metastases, as patients with metastases showed significantly higher levels of BAFF and a correlation with metastatic burden was observed. Positive BAFF staining was also found in UM tissue specimens, indicating a possible role of the BAFF signaling pathway in UM progression.
Purpose While B-cell activating factor (BAFF) was identified to promote the invasion in other malignancies, its role in the progression of uveal melanoma (UM) still remains unexplored. Here, we analysed the serum level of BAFF in UM patients with regard to its significance as biomarker for the metastases. Methods In this retrospective study, serum BAFF levels in 173 UM patients (36 with metastases and 137 without), and 23 healthy controls were measured with a multiplexed sandwich ELISA system and then correlated with clinicopathological characteristics such as primary tumor size, tumor location, histological cell type, sex, cancer stage, cytogenetic alterations of chromosome 3, and the metastatic burden. Immunohistochemical staining of 50 UM tissue specimens was also performed to evaluate the expression of BAFF and its receptors BAFF-R and TACI. Results The metastatic patients were identified to have significantly higher serum BAFF levels (mean +/- SD, 1520.8 +/- 1182.1 pg/ml) than those without metastases (950.4 +/- 494.6 pg/ml) and controls (810.3 +/- 140.5 pg/ml). While no distinctions were detected with regard to tumor location, histological cell type, gender, and monosomy 3, the patients in cancer stages II, III, and IV displayed higher serum BAFF levels than those in stage I. The serum BAFF level was significantly correlated with the metastatic burden. The serum BAFF level of 1120 pg/ml was identified to have the best performance for distinguishing the metastatic patients from non-metastatic patients. In the kinetic study, we noticed that 20.8% of the analysed patients already demonstrated elevated serum BAFF concentrations before the clinical diagnosis of metastases. Positive BAFF staining was detected in the cytoplasm of single tumor cells (in 13 specimens), macrophages (in 12 specimens), and tumor-infiltrating lymphocytes (TILs) (in 13 specimens). The expressions of BAFF-R and TACI were also observed in 17 and 36 of the 50 tested UM specimens, respectively. Conclusions Our study first suggests that BAFF might be a promising serum marker for the detection of UM metastases.

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