Depression enhanced the production of autoantibodies against 16α‑hydroxyestrone-estrogen receptor adduct in breast cancer

Abstract

Mentally depressed breast cancer (MDBC) patients expressed estrogen receptor (ER) and 16α‑hydroxyestrone (16α‑OHE1) is directly responsible for causing breast cancer (BC). This study aimed to identify whether depression in breast cancer patients enhanced the production of autoantibodies against 16α‑OHE1-ER adduct in breast cancer patients. The antibodies in the serum of 65 breast cancer patients (including 35 MDBC) and 40 control subjects were screened by direct binding, inhibition enzyme-linked immunosorbent assay (ELISA), and quantitative precipitin titration. Competition ELISA was also utilized for the estimation of 16α‑OHE1 in the serum of 30 cancer patients. Autoantibodies from MDBC showed strong recognition to 16α‑OHE1-ER in comparison to overall breast cancer patients (p < 0.05) and control subjects (p < 0.001). Although breast cancer sera showed high binding to 16α‑OHE1-ER in comparison to ER (p < 0.05) or 16α‑OHE1 (p < 0.001), the relative affinities of autoantibodies for 16α‑OHE1-ER were found to be 1.38 × 10−7 and 1.23 × 10−7 for breast cancer and MDBC patients respectively. No significant difference, either in the level of 16α‑OHE1 or 2‑hydroxyestrone/16α‑OHE1 ratio, was observed in the serum of cancer patients compared with controls, although inflammatory cytokines (IL-6, TNF-α) were significantly high in these patients. Depression in breast cancer patients augments the production of autoantibodies against 16α‑OHE1-ER through the generation of inflammatory conditions. Depression in these patients increased the release of pro-inflammatory cytokines that generate more autoantibodies and show strong binding with 16α‑OHE1-ER.