Association of adiponectin and breast cancer with type 2 diabetes mellitus and its mechanism.

Objective To analyze the possible mechanism of adiponectin in the development of breast cancer patients with type 2 diabetes mellitus (T2DM). Methods A total of 50 breast cancer patients hospitalized in the Department of Thyroid and Breast Surgery of the First Affiliated Hospital of Anhui Medical University from January to June 2016 were selected in this study. According to whether or not combined with T2DM, the patients were divided into the breast cancer with T2DM group (20 cases) and the breast cancer without T2DM group (30 cases). The breast cancer tissue specimen of the diabetic breast cancer patients was classified as DBCC group, the normal breast tissue specimen of the diabetic breast cancer patients was classified as DBCN group, the breast cancer tissue specimen of the non-diabetic breast cancer patients was classified as BCC group, and the normal breast tissue specimen of the non-diabetic breast cancer patients was classified as BCN group. Fasting plasma glucose (FPG), fasting insulin (FINS), serum lipid, total adiponectin, and high molecular weight adiponectin were detected, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The expression of receptor for advanced glycation end products (RAGE), Cyclin D1 and NF-κB in the tissue specimens were detected by Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in each group. Group differences were compared by independent-samples t test, and the histological indicators among the four groups were analyzed by analysis of variance (ANOVA) and the LSD-t test of pairwise comparison. Results Serumadiponectin [(5.35±1.22) vs (7.29±1.90)mg/L, respectively] and high molecular weight adiponectin [(3.33±0.87) vs (4.41±1.15) mg/L, respectively] in diabetic breast cancer patients were lower than those in non-diabetic breast cancer patients (P<0.05). The correlation analysis showed that serum adiponectin level and high molecular weight adiponectin level were negatively correlated with HOMA-IR(r=-0.916, -0.950, respectively, P<0.05) and tumor size (r=-0.896, -0.909, respectively, P<0.05). The expression of both protein and mRNA of RAGE, NF-κB, Cyclin D1 in DBCC group was higher than that in BCC group and DBCN group (P<0.05). The expression of adiponectin protein and mRNA in DBCC group was lower than that in DBCN group, BCC group and BCN group (P<0.05). Pearson correlation analysis showed that serum adiponectin level was negatively correlated with the expression of RAGE, Cyclin D1 and NF-κB (P<0.05). The expression of adiponectin in breast cancer tissue was negatively correlated with the expression of RAGE, NF-κB and Cyclin D1 (P<0.05). Conclusions In the type 2 diabetic breast cancer patients, the serum adiponectin level decreased, the expression of adiponectin in cancer tissues decreased, while the expression of RAGE, Cyclin D1 and NF-κB increased. Adiponectin might play a role in the development of breast cancer patients with T2DM through RAGE-NF-κB-clyin D1 signaling pathway. [ABSTRACT FROM AUTHOR]