Purpose: Lymphedema is an irreversible disorder often seen as a postoperative side effect in breast cancer survivors. We aimed to identify serum factors that are associated with lymphedema risk in breast cancer survivors. Methods: This study recruited 60 volunteer breast cancer survivors. Participants were classified into either a CTRL group who underwent sentinel lymph node biopsy (SLNB), a RISK group who underwent axillary lymph node dissection (ALND) with removal of fewer than five lymph nodes, or an LE group who underwent ALND with removal of more than five lymph nodes. Bioimpedance was measured to determine the ratio of extracellular water (ECW) to total cellular water (TCW) and single-frequency bioimpedance analysis (SFBIA) ratios. Serum lipid profiles were compared among the groups using label-free quantitative proteomics with the nano-liquid chromatography (LC)-tandem mass spectrometer (MS/MS) and emPAI method. Results: The CTRL, RISK, and LE groups had similar body weights and body mass indexes (BMIs) (<25 kg/m2). The LE group showed a higher grade of lymphedema severity compared to the RISK and CTRL groups. Lymphedema indices such as the ECW/TCW ratio and SFBIA ratio at 1 and 5 kHz were greatly increased in the LE group. Serum total cholesterol (total-C) level was higher in the LE group without affecting atherogenic index. Serum proteomics revealed that fibronectin 1 (FN1), apolipoprotein E (ApoE), antithrombin (ANT3), and complement C4 had different abundance values among the groups. ELISA confirmed that FN1 and ApoE were significantly elevated in both the RISK and LE groups compared to the CTRL group. Conclusions: Changes in serum FN1 and ApoE levels were detected prior to changes in serum total-C level and lymphedema indices such as SFBIA ratio. Therefore, elevation in serum FN1 and ApoE concentrations could likely be used to monitor the risk of lymphedema in breast cancer survivors.
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