导致低密度脂蛋白快速内化的三元复合体成分是乳腺癌与增殖和早期复发相关的生物标志物。

IF 2 Q3 ONCOLOGY

Cancer research communications Pub Date : 2025-02-01 DOI:10.1158/2767-9764.CRC-23-0562

Elizabeth S McDonald, Tien-Chi Pan, Dhruv K Pant, Melissa A Troester, Andrew V Kossenkov, David A Mankoff, Robert H Mach, Lewis A Chodosh

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引用次数: 0

摘要

最近发现的 PGRMC1-σ2R/TMEM97-LDLR 三元复合物在胆固醇转运中发挥作用。本研究调查了该复合物的单个成分是否是预后乳腺癌的生物标志物，并确定了其在已确定的分子亚型中的表达情况。研究分析了 4463 例浸润性乳腺癌的分子和表型标志物、细胞增殖估计值和无复发生存率。利用基于基因表达特征的检测方法来估算细胞增殖。Cox比例危险度回归估算了无复发生存率，多变量Cox分析调整了细胞增殖与早期复发的关系。PGRMC1-σ2R/TMEM97-LDLR的表达按免疫组化和分子亚型、肿瘤分级和大小进行了分层。TMEM97与增殖的相关性最强，在ER+疾病中最高（r=0.712，p=6.5-200）。TMEM97和PGRMC1与早期复发风险有关，取决于它们与增殖的相关性。TMEM97的早期复发风险最高，仅见于ER+/HER2-疾病（HR1.5 [1.35,1.67]，p=5.4-14）和ER+恶性肿瘤（HR1.49 [1.31;1.68]，p=3.1-10）。在ER-/HER2-（HR 1.05 [0.88; 1.25]，p=0.63）或ER-疾病（HR1.02 [0.89; 1.17]，p=0.75）中，TMEN97的表达不会增加复发风险。与低密度脂蛋白快速内化相关的三元复合物的成分是与细胞增殖和早期复发相关的生物标志物，这应有助于指导研究在其他侵袭性疾病标志物的背景下探索它们。阐明 PGRMC1、TMEM97 和 LDLR 在乳腺癌中的作用将有助于从机理上理解增殖与胆固醇代谢在恶性转化或扩散中的相互作用。

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Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence.

Significance: This first large-scale analysis of the putative ternary complex responsible for rapid low-density lipoprotein internalization in breast cancer reveals a link between component expression and recurrence, with prognostic implications for identifying patients needing supplemental posttreatment surveillance and/or additional therapeutic approaches.

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Cancer research communications

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