文章：

胰岛素样生长因子1与胰岛素受体单核苷酸变异与HER2阴性乳腺癌患者在新辅助化疗联合或不联合模拟禁食饮食治疗中的反应相关（BOOG 2013-04 DIRECT试验）

IGF1 and Insulin Receptor Single Nucleotide Variants Associated with Response in HER2-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy with or without a Fasting Mimicking Diet (BOOG 2013-04 DIRECT Trial)

原文发布日期：17 December 2023

DOI: 10.3390/cancers15245872

类型: Article

开放获取: 是

英文摘要：

Aim: We aimed to investigate associations betweenIGF1RandINSRsingle nucleotide variants (SNVs) and clinical response in patients with breast cancer treated with neoadjuvant chemotherapy with or without a fasting mimicking diet (FMD) from the DIRECT trial (NCT02126449), since insulin-like growth factor 1 (IGF1) and the insulin pathway are heavily involved in tumor growth and progression. Methods: Germline DNA from 113 patients was tested for 17 systematically selected candidate SNVs inIGF1RandINSRwith pathological and radiological response. Results:IGF1Rvariants A > G (rs3743259) and G > A (rs3743258) are associated with worse pathological response compared to reference allelesp= 0.002, OR = 0.42 (95%CI: 0.24; 0.73);p= 0.0016; OR = 0.40 (95%CI: 0.23; 0.70).INSRT > C (rs1051690) may be associated with worse radiological responsep= 0.02, OR = 2.92 (95%CI: 1.16; 7.36), although not significant after Bonferroni correction. Exploratory interaction analysis suggests thatIGF1RSNVs rs2684787 and rs2654980 interact negatively with the FMD group regarding radiological responsep= 0.036, OR = 5.13 (95%CI: 1.12; 23.63);p= 0.024, OR = 5.71 (95%CI: 1.26; 25.85). Conclusions: TheIGF1Rvariants rs3743259 and rs3743258 are negatively associated with pathological response in this cohort, suggesting potential relevance as a predictive biomarker. Further research is needed to validate these findings and elucidate the underlying mechanisms and interaction with FMD.

摘要翻译： 

目的：本研究旨在探讨IGF1R与INSR单核苷酸变异（SNVs）与乳腺癌患者临床反应之间的关联。研究对象来自DIRECT试验（NCT02126449）中接受新辅助化疗联合或不联合模拟禁食饮食（FMD）治疗的患者。由于胰岛素样生长因子1（IGF1）和胰岛素通路在肿瘤生长和进展中发挥重要作用，我们对此进行了深入分析。方法：对113例患者的种系DNA进行了检测，系统筛选了IGF1R和INSR中的17个候选SNVs，并结合病理及影像学反应进行评估。结果：与参考等位基因相比，IGF1R变异A > G（rs3743259）和G > A（rs3743258）与较差的病理反应相关（p=0.002，OR=0.42，95%CI：0.24-0.73；p=0.0016，OR=0.40，95%CI：0.23-0.70）。INSR T > C（rs1051690）可能与较差的影像学反应相关（p=0.02，OR=2.92，95%CI：1.16-7.36），但经Bonferroni校正后未达到显著性水平。探索性交互作用分析表明，在影像学反应方面，IGF1R SNVs rs2684787和rs2654980与FMD组存在负向交互作用（p=0.036，OR=5.13，95%CI：1.12-23.63；p=0.024，OR=5.71，95%CI：1.26-25.85）。结论：在本队列中，IGF1R变异rs3743259和rs3743258与病理反应呈负相关，提示其可能作为预测性生物标志物。未来需进一步研究以验证这些发现，并阐明其潜在机制及与FMD的交互作用。

原文链接：

IGF1 and Insulin Receptor Single Nucleotide Variants Associated with Response in HER2-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy with or without a Fasting Mimicking Diet (BOOG 2013-04 DIRECT Trial)