Female Serum HER2 Expression: Its Association With Metabolic Syndrome and Treatment Drug Response

To investigate the association between serum human epidermal growth factor receptor 2 (HER2) levels and metabolic syndrome (MS) in women and to explore the relationship between HER2 and the use of commonly prescribed metabolic medications.

A total of 532 women who visited Nanjing Drum Tower Hospital between January 2021 and January 2023 were enrolled. Participants were classified into a non-MS group (n = 278) and an MS group (n = 254) according to the diagnostic criteria of the Chinese Diabetes Society (2020 edition). General characteristics and serum HER2 levels were compared between groups. Based on serum HER2 levels, participants were further categorized into quartiles (Q1 [< 7.4 ng/mL], Q2 [7.4-8.5 ng/mL], Q3 [8.6-9.9 ng/mL], and Q4 [> 9.9 ng/mL]), and clinical parameters were compared among these groups. Spearman correlation analysis was performed to examine the relationships between HER2, MS-related indicators, and medication use. Logistic regression analysis was conducted to identify independent risk factors for MS.

Serum HER2 levels were significantly higher in the MS group compared with the non-MS group (8.10 [7.10-9.10] vs. 9.25 [8.10-10.80] ng/mL, p < 0.001). The prevalence of MS increased progressively across HER2 quartiles: 31.30% (Q1), 36.43% (Q2), 50.00% (Q3), and 72.39% (Q4) (p < 0.001). Serum HER2 levels were positively correlated with body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), fasting serum insulin (FINS), fasting C-peptide (FCP), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) (all p < 0.001) and negatively correlated with age, high-density lipoprotein cholesterol (HDL-C), and the use of renin-angiotensin system inhibitors and statins (all p < 0.001). Logistic regression analysis showed that higher HER2 levels remained a significant risk factor for MS after adjustment for confounders, and compared with Q1, the risk of MS in Q4 remained significantly higher in fully adjusted models.

The use of renin-angiotensin system-targeting antihypertensive agents or statins was associated with significantly reduced serum HER2 levels. Increasing serum HER2 levels correlated with a higher prevalence of MS, suggesting that elevated HER2 may serve as an independent risk factor and a potential biomarker for MS in women.