Zheng Yunfeng, Yang Fan, Wu Jie
Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Centre for Lipid Research & Chongqing Key Laboratory of Metabolism on Lipid and Glucose, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Int J Biol Markers. 2025 Mar;40(1):3-11. doi: 10.1177/03936155241304433. Epub 2024 Dec 16.
BackgroundThis study aims to investigate the mutation status and protein expression of low-density lipoprotein receptor-related protein 1B (LRP1B) in endometrial cancer, and analyze its association with lymph node metastasis (LNM) in endometrial cancer.MethodsTargeted next-generation sequencing (NGS) was conducted on both tumor tissues and paired blood DNA obtained from 94 endometrial cancer patients, followed by comprehensive analysis. Additionally, immunohistochemistry (IHC) was used to explore the correlation between LRP1B protein expression levels, its gene mutation status, and LNM.Results mutation was observed in 19 patients (20.2%). Our results revealed that mutation frequencies were significantly different between endometrial cancer with or without LNM (= 0.038). Multivariate analysis indicated that mutation was a favorable predictor (odds ratio 0.09; 95% confidence interval 0.01-0.95; = 0.045) for LNM in endometrial cancer. Further analysis revealed that combination of mutation with clinical variants (LVSI and histological subtype) yielded a higher area under the curve value of 0.871) and patients harboring mutated-type were less likely to develop LNM. On integrated analysis, the concordance between NGS and LRP1B IHC was 73.3%.ConclusionsThis study utilizes targeted NGS to uncover the relationship between mutation and LNM status, contributing to the development of primary prevention and proactive treatment strategies.
背景
本研究旨在调查子宫内膜癌中低密度脂蛋白受体相关蛋白1B(LRP1B)的突变状态和蛋白表达,并分析其与子宫内膜癌淋巴结转移(LNM)的相关性。
方法
对94例子宫内膜癌患者的肿瘤组织和配对的血液DNA进行靶向二代测序(NGS),随后进行综合分析。此外,采用免疫组织化学(IHC)方法探讨LRP1B蛋白表达水平、基因突变状态与LNM之间的相关性。
结果
19例患者(20.2%)检测到突变。我们的结果显示,有或无LNM的子宫内膜癌之间的突变频率存在显著差异(P = 0.038)。多因素分析表明,突变是子宫内膜癌LNM的一个有利预测指标(优势比0.09;95%置信区间0.01 - 0.95;P = 0.045)。进一步分析显示,突变与临床变量(淋巴血管间隙浸润和组织学亚型)相结合产生了更高的曲线下面积值(0.871),且携带突变型的患者发生LNM的可能性较小。综合分析显示,NGS与LRP1B IHC之间的一致性为73.3%。
结论
本研究利用靶向NGS揭示了突变与LNM状态之间的关系,有助于制定一级预防和积极治疗策略。