Head and Neck Breast Surgery, The Yuebei People's Hospital of Shaoguan, Guangdong Province, 512025, Shaoguan, China.
Department of Anesthesiology, Maternal and Child Health Hospital of Hubei Province, Hubei Province, 430070, Wuhan, China.
BMC Cancer. 2022 Aug 13;22(1):886. doi: 10.1186/s12885-022-09959-6.
Obesity is a high-risk factor for development and poor prognosis of triple-negative breast cancer (TNBC), which was considered as a high malignant and poor clinical outcome breast cancer subtype. TNBC proliferation and migration regulated by obesity is complex. Here, we studied effects of cytokines secreted from adipose tissue on development of TNBC.
Forty postmenopausal cases by Yuebei People's Hospital of Shaoguan with stage I/IIA TNBC were enrolled. Cytokine concentrations were examined using ELISA analysis. Proliferation and migration of TNBC cell lines were performed using CCK8 assays and Transwell tests. The Log-rank (Mantel-Cox) test, two-tailed Mann-Whitney U test and two-tailed unpaired t test were performed using GraphPad Prism 8.4.2.
Survival analysis indicated that obese patients with TNBC had worse disease free survival (DFS) as compared with normal weight group (Hazard Ratio 4.393, 95% confidence interval (CI) of ratio 1.071-18.02, p < 0.05). Obese patients with TNBC had severe insulin resistance and high plasma triglycerides. However, plasma adiponectin concentration was decreased and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentration was increased in obese TNBC patients as compared with the nonobese group. The similar results were found in the cytokine secretion from adipose tissues and insulin-resistant adipocytes. The secretion of adipose tissue from obese TNBC patients could promote proliferation and migration of TNBC cell lines, including MDA-MB-157, MDA-MB-231, MDA-MB-453 and HCC38 cells. These TNBC cell lines co-incubated with insulin-resistant 3T3-L1 adipocytes or supplementing these cytokines medium also exhibited increase of proliferative and migratory capacity.
TNBC patients with obesity had worse prognosis compared with the normal weight groups. Alteration of cytokines secreted from adipose tissues mediated proliferation and migration of TNBC, leading to tumor progression in TNBC patients with obesity.
肥胖是三阴性乳腺癌（TNBC）发生和预后不良的高危因素，TNBC 被认为是一种恶性程度高、临床结局差的乳腺癌亚型。肥胖调节的 TNBC 增殖和迁移是复杂的。在这里，我们研究了脂肪组织分泌的细胞因子对 TNBC 发展的影响。
纳入韶关粤北人民医院 40 例绝经后Ⅰ/ⅡA 期 TNBC 患者，采用 ELISA 分析检测细胞因子浓度。采用 CCK8 检测和 Transwell 检测 TNBC 细胞系的增殖和迁移。使用 GraphPad Prism 8.4.2 进行 Log-rank（Mantel-Cox）检验、双侧 Mann-Whitney U 检验和双侧非配对 t 检验。
生存分析表明，与正常体重组相比，肥胖 TNBC 患者无病生存期（DFS）更差（风险比 4.393，比值 95%置信区间（CI）为 1.071-18.02，p<0.05）。肥胖 TNBC 患者存在严重的胰岛素抵抗和高血浆甘油三酯，而肥胖 TNBC 患者的血浆脂联素浓度降低，白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）浓度升高与非肥胖组相比。在肥胖 TNBC 患者的脂肪组织和胰岛素抵抗脂肪细胞中也发现了类似的结果。肥胖 TNBC 患者的脂肪组织分泌可促进 TNBC 细胞系，包括 MDA-MB-157、MDA-MB-231、MDA-MB-453 和 HCC38 细胞的增殖和迁移。这些 TNBC 细胞系与胰岛素抵抗的 3T3-L1 脂肪细胞共孵育或补充这些细胞因子培养基也表现出增殖和迁移能力的增加。
与正常体重组相比，肥胖的 TNBC 患者预后更差。脂肪组织分泌的细胞因子改变介导 TNBC 的增殖和迁移，导致肥胖 TNBC 患者的肿瘤进展。
