Zheng Jing, Suo Chen, Wu Yan, Cao Baokun, Yuan Ziyu, Jiang Yanfeng, Liu Zhenqiu, Ye Weimin, Yang Haomin, Chen Xingdong
Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China.
Department of Epidemiology, School of Public Health, and the Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China.
NPJ Precis Oncol. 2025 Jul 15;9(1):238. doi: 10.1038/s41698-025-01019-z.
Immuno-oncology biomarkers are promising tools for cancer risk assessment and early detection. To identify and validate their associations with breast cancer, nested case-control studies within the Taizhou Longitudinal Study (TZL) cohort and the UK biobank Pharma Proteomics Project (UKB-PPP) were conducted, comprising 195 and 881 incident breast cancer patients, together with their matched controls. Among the 92 plasma proteins tested by the Olink Immuno-oncology panel, 11 proteins were associated with breast cancer risk in the TZL cohort after multiple testing correction. Notably, hepatocyte growth factor (HGF) was validated in the UKB-PPP, particularly among postmenopausal women (OR = 1.13, 95% CI = 1.03-1.24). The association was stronger with Estrogen Receptor-negative breast cancer and confirmed by Mendelian Randomization analysis. Additionally, HGF mediated the effects of Healthy Lifestyle Index (27.17%) and BMI (19.79%) on breast cancer risk. Therefore, HGF could be an intervention target by either medicines or lifestyle changes to improve the prevention and treatment of breast cancer.
免疫肿瘤生物标志物是用于癌症风险评估和早期检测的有前景的工具。为了识别和验证它们与乳腺癌的关联，在泰州纵向研究（TZL）队列和英国生物银行药物蛋白质组学项目（UKB-PPP）中开展了巢式病例对照研究，包括195例和881例新发乳腺癌患者及其匹配对照。在通过Olink免疫肿瘤检测板检测的92种血浆蛋白中，经过多重检验校正后，11种蛋白与TZL队列中的乳腺癌风险相关。值得注意的是，肝细胞生长因子（HGF）在UKB-PPP中得到验证，尤其是在绝经后女性中（OR = 1.13，95%CI = 1.03 - 1.24）。该关联在雌激素受体阴性乳腺癌中更强，并通过孟德尔随机化分析得到证实。此外，HGF介导了健康生活方式指数（27.17%）和体重指数（19.79%）对乳腺癌风险的影响。因此，HGF可能是通过药物或生活方式改变来改善乳腺癌预防和治疗的干预靶点。
