Accelerated PCB clearance in thyroid cancer: BRAF^V600E mutation links reduced serum concentrations to tumor severity

This study investigated the paradoxical reductions in serum polychlorinated biphenyl (PCB) concentrations among thyroid cancer patients, with emphasis on the role of the oncogenic B-Raf proto-oncogene, serine/threonine kinase V600E （BRAF^V600E）mutation. Serum samples from 55 thyroid disease patients (44 cancer, 11 non-cancer) in Shanghai were analyzed for 12 PCB congeners using GC-MS/MS with isotope dilution. Thyroid cancer patients exhibited significantly lower levels of indicator PCBs (ΣIn-PCBs: PCB 28, 52, 138, 153, 180) compared to non-cancer controls (median 3.3 vs 9.9 ng/g lipid, p = 0.003), particularly PCB 138,153,180 (p < 0.01). Critically, BRAF^V600E-mutant cancer patients showed further reductions in PCB 138,153 and 180 levels (p < 0.05) compared to non-mutant/benign cases. MedianΣIn-PCBs concentrations were 5-6 times higher than those of dioxin-like PCBs (ΣDL-PCBs) in all samples (p < 0.001). These results indicate that decreased serum PCB levels in thyroid cancer patients, which are more pronounced in the presence of the BRAF^V600E mutation, may reflect enhanced tumor-related PCBs metabolism. This finding implies the potential utility of reduced PCB levels as a biomkarker for metabolic dysregulation in thyroid malignancy, and is worthy of further exploration of the possible role of PCB metabolites in the thyroid occurrence of thyroid cancer.